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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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24 pages, 1192 KiB  
Review
Salmonella Infection in Pigs: Disease, Prevalence, and a Link between Swine and Human Health
by Laura Soliani, Gianluca Rugna, Alice Prosperi, Chiara Chiapponi and Andrea Luppi
Pathogens 2023, 12(10), 1267; https://doi.org/10.3390/pathogens12101267 - 21 Oct 2023
Cited by 6 | Viewed by 4497
Abstract
Salmonella is one of the most spread foodborne pathogens worldwide, and Salmonella infections in humans still represent a global health burden. The main source of Salmonella infections in humans is represented by contaminated animal-derived foodstuffs, with pork products being one of the most [...] Read more.
Salmonella is one of the most spread foodborne pathogens worldwide, and Salmonella infections in humans still represent a global health burden. The main source of Salmonella infections in humans is represented by contaminated animal-derived foodstuffs, with pork products being one of the most important players. Salmonella infection in swine is critical not only because it is one of the main causes of economic losses in the pork industry, but also because pigs can be infected by several Salmonella serovars, potentially contaminating the pig meat production chain and thus posing a significant threat to public health globally. As of now, in Europe and in the United States, swine-related Salmonella serovars, e.g., Salmonella Typhimurium and its monophasic variant Salmonella enterica subsp. enterica 1,4,[5],12:i:-, are also frequently associated with human salmonellosis cases. Moreover, multiple outbreaks have been reported in the last few decades which were triggered by the consumption of Salmonella-contaminated pig meat. Throughout the years, changes and evolution across the pork industry may have acted as triggers for new issues and obstacles hindering Salmonella control along the food chain. Gathered evidence reinforces the importance of coordinating control measures and harmonizing monitoring programs for the efficient control of Salmonella in swine. This is necessary in order to manage outbreaks of clinical disease in pigs and also to protect pork consumers by controlling Salmonella subclinical carriage and shedding. This review provides an update on Salmonella infection in pigs, with insights on Salmonella ecology, focusing mainly on Salmonella Choleraesuis, S. Typhimurium, and S. 1,4,[5],12:i:-, and their correlation to human salmonellosis cases. An update on surveillance methods for epidemiological purposes of Salmonella infection in pigs and humans, in a “One Health” approach, will also be reported. Full article
(This article belongs to the Special Issue Swine Bacterial Pathogens from a One Health Perspective)
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12 pages, 1900 KiB  
Article
Epidemiological Characteristics of Carbapenem-Resistant Enterobacterales in Japan: A Nationwide Analysis of Data from a Clinical Laboratory Center (2016–2022)
by Kentarou Takei, Miho Ogawa, Ryuji Sakata and Hajime Kanamori
Pathogens 2023, 12(10), 1246; https://doi.org/10.3390/pathogens12101246 - 16 Oct 2023
Cited by 3 | Viewed by 1789
Abstract
In Japan, nationwide epidemiological surveys on carbapenem-resistant Enterobacterales (CREs), including comprehensive information, are scarce, with most data available only through public reports. This study analyzed data on the Enterobacterales family collected from nationwide testing centers between January 2016 and December 2022, focusing on [...] Read more.
In Japan, nationwide epidemiological surveys on carbapenem-resistant Enterobacterales (CREs), including comprehensive information, are scarce, with most data available only through public reports. This study analyzed data on the Enterobacterales family collected from nationwide testing centers between January 2016 and December 2022, focusing on isolates that met the criteria for CRE in Japan based on drug susceptibility. We investigated 5,323,875 Enterobacterales isolates of 12 different species; among 4696 (0.09%) CRE strains, the proportion of major CRE isolates was as follows: Escherichia coli, 31.3%; Klebsiella pneumoniae, 28.0%; Enterobacter cloacae, 18.5%; and Klebsiella aerogenes, 6.7%. Moreover, over a 7-year period, Providencia rettgeri, E. cloacae, K. aerogenes, and K. pneumoniae demonstrated relatively high CRE percentages of 0.6% (156/26,185), 0.47% (869/184,221), 0.28% (313/110,371), and 0.17% (1314/780,958), respectively. The number of CRE strains isolated from different samples was as follows: urine, 2390; respiratory specimens, 1254; stool, 425; blood, 252; others, 375. In the broader context, including colonization, the predominant isolates of CREs collected at nationwide testing centers are E. coli and K. pneumoniae. Furthermore, recently, attention has been directed toward less common CRE species, such as Klebsiella oxytoca and Providencia rettgeri, and thus, it might be necessary to continue monitoring these less common species. Full article
(This article belongs to the Special Issue Detection and Epidemiology of Drug-Resistant Bacteria)
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15 pages, 1636 KiB  
Article
Characterization of mRNA Signature in Milk Small Extracellular Vesicles from Cattle Infected with Bovine Leukemia Virus
by Md. Matiur Rahman, Hinata Ishikawa, Marika Yamauchi, Shigeo Takashima, Yuji O. Kamatari, Kaori Shimizu, Ayaka Okada and Yasuo Inoshima
Pathogens 2023, 12(10), 1239; https://doi.org/10.3390/pathogens12101239 - 13 Oct 2023
Cited by 2 | Viewed by 2881
Abstract
This study aimed to characterize the mRNA signature of milk small extracellular vesicles (sEVs) from BLV-infected cattle. A total of 23 mRNAs, which showed greater abundance in milk sEVs from BLV-infected cattle compared to those from BLV-uninfected (control) cattle, were identified through microarray [...] Read more.
This study aimed to characterize the mRNA signature of milk small extracellular vesicles (sEVs) from BLV-infected cattle. A total of 23 mRNAs, which showed greater abundance in milk sEVs from BLV-infected cattle compared to those from BLV-uninfected (control) cattle, were identified through microarray analyses conducted in our previous study. To assess the significance of these differences in mRNA abundance, milk was collected from six control cattle and twenty-six cattle infected with BLV. The infected cattle were categorized into two distinct groups based on their proviral loads: a group of eight cattle with low proviral loads (LPVL), characterized by <10,000 copies per 105 white blood cells (WBC), and a group of eighteen cattle with high proviral loads (HPVL), marked by ≥10,000 copies per 105 WBC. The qPCR analysis quantified 7 out of 23 mRNAs, including BoLA, CALB1, IL33, ITGB2, MYOF, TGFBR1, and TMEM156, in the milk sEVs from control cattle, LPVL cattle, and HPVL cattle. Significantly, the average relative expression of CALB1 mRNA in milk sEVs was higher in LPVL cattle compared to HPVL cattle and control cattle (p < 0.05), while it was relatively lower in HPVL cattle compared to LPVL cattle and control cattle (p > 0.05). Likewise, the average relative expression of TMEM156 mRNA in milk sEVs was significantly higher in LPVL cattle compared to HPVL cattle (p < 0.05), and relatively lower in HPVL cattle compared to LPVL cattle and control cattle (p > 0.05). The results indicate distinct patterns of CALB1 and TMEM156 mRNA levels in milk sEVs, with higher levels observed in LPVL cattle and lower levels in HPVL cattle. The current study could provide essential information to comprehend the complexities during the progression of BLV infection and direct the exploration of mRNA biomarkers for monitoring the clinical stage of BLV infection. Full article
(This article belongs to the Special Issue Diagnostics of Animal Viral Infectious Diseases)
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13 pages, 1804 KiB  
Article
Human Papillomavirus Genotype Richness and the Biodiversity of Squamous and Glandular Cervical Dysplasias: A Cross-Sectional Study
by Elisa Gozzini, Davide Radice, Fabio Bottari, Sara Boveri, Maria Elena Guerrieri, Eleonora Petra Preti, Noemi Spolti, Mariacristina Ghioni, Federico Ferrari and Anna Daniela Iacobone
Pathogens 2023, 12(10), 1234; https://doi.org/10.3390/pathogens12101234 - 11 Oct 2023
Viewed by 2818
Abstract
The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of [...] Read more.
The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of precancerous lesions. We conducted a cross-sectional analysis involving 469 women who attended the Colposcopy Unit at the European Institute of Oncology in Milan, Italy, from December 2006 to December 2014. HPV type richness was measured as the number of different genotypes per patient. We calculated the associations between richness and age, as well as histologic grade, along with Simpson’s biodiversity index for cervical dysplasias. We observed significant inverse relationships between the richness of high-risk (HR) genotypes and both age (p = 0.007) and histologic grade (p < 0.001). Furthermore, as the histologic grade increased, the mean biodiversity index of cervical dysplasias decreased, with exceptions noted in cases of normal histology and adenocarcinoma in situ. Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. These findings suggest that HPV genotype richness and the biodiversity of cervical dysplasias may play a crucial role in predicting the risk of high-grade cervical lesions, enabling personalized management of precancers. Full article
(This article belongs to the Special Issue Epidemiology of Human Papillomavirus Infection)
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17 pages, 11271 KiB  
Article
In Vivo Efficacy of Curcumin and Curcumin Nanoparticle in Trypanosoma congolense, Broden 1904 (Kinetoplastea: Trypanosomatidae)-Infected Mice
by Nthatisi Innocentia Molefe-Nyembe, Oluyomi Stephen Adeyemi, Daisuke Kondoh, Kentaro Kato, Noboru Inoue and Keisuke Suganuma
Pathogens 2023, 12(10), 1227; https://doi.org/10.3390/pathogens12101227 - 9 Oct 2023
Viewed by 1389
Abstract
Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. [...] Read more.
Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. b. brucei, and T. evansi. Additionally, CUR and CUR-nanoparticle anti-Trypanosoma efficacy were assessed in vivo against T. congolense. All the CUR-nanoparticles were two folds more effective on the T. congolense as compared to CUR in vitro, with recorded efficacy of 3.67 ± 0.31; 7.61 ± 1.22; and 6.40 ± 3.07 μM, while the CUR-nanoparticles efficacy was 1.56 ± 0.50; 28.16 ± 9.43 and 13.12 ± 0.13 μM on T. congolense, T. b. brucei, and T. evansi, respectively. Both CUR and CUR-nanoparticles displayed moderate efficacy orally. The efficacy of CUR and CUR-nanoparticles in vivo was influenced by solubility, presence of food, and treatment period. CUR-treated mice were not cured of the infection; however, the survival rate of the orally treated mice was significantly prolonged as compared with intraperitoneal-treated mice. CUR-nanoparticles resulted in significant suppression of parasitemia even though relapsed was observed. In conclusion, CUR and CUR-nanoparticles possess moderate efficacy orally on the trypanosomes as compared to the intraperitoneal treatment. Full article
(This article belongs to the Special Issue Parasitic Infections and Diseases of Domestic Animals)
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15 pages, 5891 KiB  
Review
An Update on the Current State of SARS-CoV-2 Mac1 Inhibitors
by Joseph J. O’Connor, Dana Ferraris and Anthony R. Fehr
Pathogens 2023, 12(10), 1221; https://doi.org/10.3390/pathogens12101221 - 7 Oct 2023
Cited by 4 | Viewed by 1719
Abstract
Non-structural protein 3 (nsp3) from all coronaviruses (CoVs) contains a conserved macrodomain, known as Mac1, that has been proposed as a potential therapeutic target for CoVs due to its critical role in viral pathogenesis. Mac1 is an ADP-ribose binding protein and ADP-ribosylhydrolase that [...] Read more.
Non-structural protein 3 (nsp3) from all coronaviruses (CoVs) contains a conserved macrodomain, known as Mac1, that has been proposed as a potential therapeutic target for CoVs due to its critical role in viral pathogenesis. Mac1 is an ADP-ribose binding protein and ADP-ribosylhydrolase that promotes replication and blocks IFN responses, though the precise mechanisms it uses to carry out these functions remain unknown. Over the past 3 years following the onset of COVID-19, several groups have used high-throughput screening with multiple assays and chemical modifications to create unique chemical inhibitors of the SARS-CoV-2 Mac1 protein. Here, we summarize the current efforts to identify selective and potent inhibitors of SARS-CoV-2 Mac1. Full article
(This article belongs to the Special Issue ADP-Ribosylation in Pathogens)
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11 pages, 439 KiB  
Article
Neurocysticercosis Diagnosis in a Non-Endemic Country: France
by Ines Zemmour, Marie-Fleur Durieux, Etienne Herault, Célia Rouges, Barbara Šoba, Aurélien Mercier, Frédéric Ariey, Pierre-Marie Preux, Hélène Yera and on behalf of Collaborators Group
Pathogens 2023, 12(10), 1205; https://doi.org/10.3390/pathogens12101205 - 29 Sep 2023
Cited by 1 | Viewed by 1320
Abstract
Diagnosing neurocysticercosis (NCC) is difficult due to its variable clinical presentations and the different imaging techniques used to detect brain damage. This study aimed to evaluate the use of cerebrospinal fluid serology and PCR for diagnosing biological neurocysticercosis in a non-endemic country. We [...] Read more.
Diagnosing neurocysticercosis (NCC) is difficult due to its variable clinical presentations and the different imaging techniques used to detect brain damage. This study aimed to evaluate the use of cerebrospinal fluid serology and PCR for diagnosing biological neurocysticercosis in a non-endemic country. We tested samples from patients living in France with suspected NCC and confirmed that 45 of the patients presented with the disease. A total of 89% of patients had previously traveled to countries where the disease was endemic. The sensitivity of Western blots compared to ELISA was not significantly different (80% vs. 60%) (p > 0.05), and neither was the sensitivity of Western blots vs. PCR (78% vs. 56%) (p > 0.05). The PCR sensitivity was 78% and 47% in definitive NCC and in probable NCC. PCR tests using cerebrospinal fluid should be considered as a diagnostic criterion for identifying NCC. Full article
(This article belongs to the Special Issue Recent Advances in Taeniasis and Cysticercosis)
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34 pages, 2450 KiB  
Review
The In Vitro Antimicrobial Susceptibility of Borrelia burgdorferi sensu lato: Shedding Light on the Known Unknowns
by Klaus-Peter Hunfeld, Peter Kraiczy, Douglas E. Norris and Benedikt Lohr
Pathogens 2023, 12(10), 1204; https://doi.org/10.3390/pathogens12101204 - 28 Sep 2023
Cited by 1 | Viewed by 2632
Abstract
Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex that have been infected with the spirochete Borrelia burgdorferi sensu lato. Today, LB is considered the most [...] Read more.
Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex that have been infected with the spirochete Borrelia burgdorferi sensu lato. Today, LB is considered the most important human tick-borne illness in the Northern Hemisphere. The causative agent was identified and successfully isolated in 1982 and, shortly thereafter, antibiotic treatment was found to be safe and efficacious. Since then, various in vitro studies have been conducted in order to improve our knowledge of the activity of antimicrobial agents against B. burgdorferi s. l. The full spectrum of in vitro antibiotic susceptibility has still not been defined for some of the more recently developed compounds. Moreover, our current understanding of the in vitro interactions between B. burgdorferi s. l. and antimicrobial agents, and their possible mechanisms of resistance remains very limited and is largely based on in vitro susceptibility experiments on only a few isolates of Borrelia. Even less is known about the possible mechanisms of the in vitro persistence of spirochetes exposed to antimicrobial agents in the presence of human and animal cell lines. Only a relatively small number of laboratory studies and cell culture experiments have been conducted. This review summarizes what is and what is not known about the in vitro susceptibility of B. burgdorferi s. l. It aims to shed light on the known unknowns that continue to fuel current debates on possible treatment resistance and mechanisms of persistence of Lyme disease spirochetes in the presence of antimicrobial agents. Full article
(This article belongs to the Special Issue Pathogenesis, Epidemiology, Host Response and Control of Lyme Disease and Other Tick-Borne Diseases)
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14 pages, 995 KiB  
Review
Epidemiology and Transmission of Theileria orientalis in Australasia
by Biniam T. Lakew, Steve Eastwood and Stephen W. Walkden-Brown
Pathogens 2023, 12(10), 1187; https://doi.org/10.3390/pathogens12101187 - 22 Sep 2023
Cited by 4 | Viewed by 1707
Abstract
Oriental theileriosis, a disease primarily impacting cattle is caused by an apicomplexan hemoprotozoan parasite, Theileria orientalis. It has now become established in the Australasia region. The organism was long considered a benign cause of persistent infections; however, an increase in clinical outbreaks [...] Read more.
Oriental theileriosis, a disease primarily impacting cattle is caused by an apicomplexan hemoprotozoan parasite, Theileria orientalis. It has now become established in the Australasia region. The organism was long considered a benign cause of persistent infections; however, an increase in clinical outbreaks since 2006 in the eastern Australian states and New Zealand was associated with the identification of the pathogenic Ikeda (Type 2) and Chitose (Type 1) genotypes. Unlike the pathogenic T. parva and T. annulate, which target leucocytes, clinical manifestation with T. orientalis is due to its effects on erythrocytes, with the infection sometimes designated as Theileria associated bovine anemia (TABA). In Australia and New Zealand, the tick Haemaphysalis longicornis is the principal vector, though other Haemaphysalis species are also likely vectors. The endemic status of infection with pathogenic genotypes in areas with low or absent tick populations is an apparent paradox that may be attributable to alternative modes of transmission, such as mechanical transmission by hematophagous insects (lice, mosquitoes, and biting flies), vertical transmission, and transmission via iatrogenic means. This review addresses the evidence for the different modes of transmission of T. orientalis with particular focus on the reported and potential vectors in Australasia. Full article
(This article belongs to the Special Issue Bovine Theileriosis Caused by the Theileria orientalis Group)
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20 pages, 2371 KiB  
Review
Rift Valley Fever Virus—Infection, Pathogenesis and Host Immune Responses
by Niranjana Nair, Albert D. M. E. Osterhaus, Guus F. Rimmelzwaan and Chittappen Kandiyil Prajeeth
Pathogens 2023, 12(9), 1174; https://doi.org/10.3390/pathogens12091174 - 19 Sep 2023
Cited by 10 | Viewed by 3236
Abstract
Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate [...] Read more.
Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate proinflammatory immune responses and lead to attenuation of the virus. Upon infection, virus-specific antibodies and T cells are induced that may afford protection against subsequent infections. Thus, all arms of the adaptive immune system contribute to prevention of disease progression. These findings will aid the design of vaccines using the currently available platforms. Vaccine candidates have shown promise in safety and efficacy trials in susceptible animal species and these may contribute to the control of RVFV infections and prevention of disease progression in humans and ruminants. Full article
(This article belongs to the Special Issue Current Advances in Flavivirus and Other Arboviruses)
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14 pages, 2418 KiB  
Article
Interferon-λ Activates a Differential Response in Peripheral Neurons That Is Effective against Alpha Herpesvirus Infections
by Stephanie Salazar, Khanh T. Y. Luong, Taulima Nua and Orkide O. Koyuncu
Pathogens 2023, 12(9), 1142; https://doi.org/10.3390/pathogens12091142 - 7 Sep 2023
Cited by 3 | Viewed by 1802
Abstract
Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is [...] Read more.
Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is not well understood. Using primary neurons cultured in compartmentalized chambers, prior studies performed on Pseudorabies virus (PRV) have demonstrated that type I and type II interferons (IFNs) induce a local antiviral response in axons via distinct mechanisms leading to a reduction in viral particle transport to the neuronal nucleus. A new class of interferons known as type III IFNs has been shown to play an immediate role against viral infection in mucosal epithelial cells. However, the antiviral effects of type III IFNs within neurons during α-HV infection are largely unknown. In this study, we focused on elucidating the antiviral activity of type III IFN against PRV neuronal infection, and we compared the interferon-stimulated gene (ISGs) induction pattern in neurons to non-neuronal cells. We found that IFN pre-exposure of both primary neurons and fibroblast cells significantly reduces PRV virus yield, albeit by differential STAT activation and ISG induction patterns. Notably, we observed that type III IFNs trigger the expression of a subset of ISGs mainly through STAT1 activation to induce an antiviral state in primary peripheral neurons. Full article
(This article belongs to the Special Issue Host–Virus Interactions in the Nervous System)
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20 pages, 4370 KiB  
Article
Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi
by Danielle Pessôa-Pereira, Breanna M. Scorza, Karen I. Cyndari, Erin A. Beasley and Christine A. Petersen
Pathogens 2023, 12(9), 1128; https://doi.org/10.3390/pathogens12091128 - 4 Sep 2023
Cited by 1 | Viewed by 2638
Abstract
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, [...] Read more.
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs. Full article
(This article belongs to the Special Issue Host-Pathogen Interactions during Leishmania Infections—a Special Issue in Honor of Prof. Dr. John David)
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20 pages, 1408 KiB  
Review
Reshaping Our Knowledge: Advancements in Understanding the Immune Response to Human Respiratory Syncytial Virus
by Federica Attaianese, Sara Guiducci, Sandra Trapani, Federica Barbati, Lorenzo Lodi, Giuseppe Indolfi, Chiara Azzari and Silvia Ricci
Pathogens 2023, 12(9), 1118; https://doi.org/10.3390/pathogens12091118 - 1 Sep 2023
Cited by 2 | Viewed by 2072
Abstract
Human respiratory syncytial virus (hRSV) is a significant cause of respiratory tract infections, particularly in young children and older adults. In this review, we aimed to comprehensively summarize what is known about the immune response to hRSV infection. We described the innate and [...] Read more.
Human respiratory syncytial virus (hRSV) is a significant cause of respiratory tract infections, particularly in young children and older adults. In this review, we aimed to comprehensively summarize what is known about the immune response to hRSV infection. We described the innate and adaptive immune components involved, including the recognition of RSV, the inflammatory response, the role of natural killer (NK) cells, antigen presentation, T cell response, and antibody production. Understanding the complex immune response to hRSV infection is crucial for developing effective interventions against this significant respiratory pathogen. Further investigations into the immune memory generated by hRSV infection and the development of strategies to enhance immune responses may hold promise for the prevention and management of hRSV-associated diseases. Full article
(This article belongs to the Special Issue Immunity to Respiratory Infections)
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14 pages, 9317 KiB  
Article
Effects of Host Plants and Their Infection Status on Acquisition and Inoculation of A Plant Virus by Its Hemipteran Vector
by Saurabh Gautam, Kiran R. Gadhave, James W. Buck, Bhabesh Dutta, Timothy Coolong, Scott Adkins, Alvin M. Simmons and Rajagopalbabu Srinivasan
Pathogens 2023, 12(9), 1119; https://doi.org/10.3390/pathogens12091119 - 1 Sep 2023
Cited by 2 | Viewed by 1575
Abstract
Whitefly, Bemisia tabaci Gennadius (B cryptic species), transmits cucurbit leaf crumple virus (CuLCrV) in a persistent fashion. CuLCrV affects several crops such as squash and snap bean in the southeastern United States. CuLCrV is often found as a mixed infection with whitefly transmitted [...] Read more.
Whitefly, Bemisia tabaci Gennadius (B cryptic species), transmits cucurbit leaf crumple virus (CuLCrV) in a persistent fashion. CuLCrV affects several crops such as squash and snap bean in the southeastern United States. CuLCrV is often found as a mixed infection with whitefly transmitted criniviruses, such as cucurbit yellow stunting disorder virus (CYSDV) in hosts such as squash, or as a single infection in hosts such as snap bean. The implications of different host plants (inoculum sources) with varying infection status on CuLCrV transmission/epidemics is not clear. This study conducted a series of whitefly mediated CuLCrV transmission experiments. In the first experiment, three plants species: squash, snap bean, and tobacco were inoculated by whiteflies feeding on field-collected mixed-infected squash plants. In the second experiment, three plant species, namely squash, snap bean, and tobacco with varying infection status (squash infected with CuLCrV and CYSDV and snap bean and tobacco infected with CuLCrV), were used as inoculum sources. In the third experiment, squash plants with differential CuLCrV accumulation levels and infection status (either singly infected with CuLCrV or mixed infected with CuLCrV and CYSDV) were used as inoculum sources. Irrespective of plant species and its infection status, CuLCrV accumulation in whiteflies was dependent upon the CuLCrV accumulation in the inoculum source plants. Furthermore, differential CuLCrV accumulation in whiteflies resulted in differential transmission, CuLCrV accumulation, and disease phenotype in the recipient squash plants. Overall, results demonstrate that whitefly mediated CuLCrV transmission between host plants follows a virus density dependent phenomenon with implications for epidemics. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)
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22 pages, 3012 KiB  
Article
Mycobacterium tuberculosis Central Metabolism Is Key Regulator of Macrophage Pyroptosis and Host Immunity
by Michelle E. Maxson, Lahari Das, Michael F. Goldberg, Steven A. Porcelli, John Chan and William R. Jacobs, Jr.
Pathogens 2023, 12(9), 1109; https://doi.org/10.3390/pathogens12091109 - 30 Aug 2023
Cited by 1 | Viewed by 2351
Abstract
Metabolic dysregulation in Mycobacterium tuberculosis results in increased macrophage apoptosis or pyroptosis. However, mechanistic links between Mycobacterium virulence and bacterial metabolic plasticity remain ill defined. In this study, we screened random transposon insertions of M. bovis BCG to identify mutants that induce pyroptotic [...] Read more.
Metabolic dysregulation in Mycobacterium tuberculosis results in increased macrophage apoptosis or pyroptosis. However, mechanistic links between Mycobacterium virulence and bacterial metabolic plasticity remain ill defined. In this study, we screened random transposon insertions of M. bovis BCG to identify mutants that induce pyroptotic death of the infected macrophage. Analysis of the transposon insertion sites identified a panel of fdr (functioning death repressor) genes, which were shown in some cases to encode functions central to Mycobacterium metabolism. In-depth studies of one fdr gene, fdr8 (BCG3787/Rv3727), demonstrated its important role in the maintenance of M. tuberculosis and M. bovis BCG redox balance in reductive stress conditions in the host. Our studies expand the subset of known Mycobacterium genes linking bacterial metabolic plasticity to virulence and also reveal that the broad induction of pyroptosis by an intracellular bacterial pathogen is linked to enhanced cellular immunity in vivo. Full article
(This article belongs to the Special Issue Biology of Mycobacterial Pathogens)
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16 pages, 2793 KiB  
Article
Evaluation of a Tetracycline-Resistant E. coli Enumeration Method for Correctly Classifying E. coli in Environmental Waters in Kentucky, USA
by Callie Boggs, Kidus Shiferawe, Eckhardt Karsten, Jayden Hamlet, S. Travis Altheide and Jason W. Marion
Pathogens 2023, 12(9), 1090; https://doi.org/10.3390/pathogens12091090 - 28 Aug 2023
Cited by 2 | Viewed by 1890
Abstract
The global concern over antimicrobial resistance (AMR) and its impact on human health is evident, with approximately 4.95 million annual deaths attributed to antibiotic resistance. Regions with inadequate water, sanitation, and hygiene face challenges in responding to AMR threats. Enteric bacteria, particularly E. [...] Read more.
The global concern over antimicrobial resistance (AMR) and its impact on human health is evident, with approximately 4.95 million annual deaths attributed to antibiotic resistance. Regions with inadequate water, sanitation, and hygiene face challenges in responding to AMR threats. Enteric bacteria, particularly E. coli, are common agents linked to AMR-related deaths (23% of cases). Culture-based methods for detecting tetracycline-resistant E. coli may be of practical value for AMR monitoring in limited resource environments. This study evaluated the ColiGlow™ method with tetracycline for classifying tetracycline-resistant E. coli. A total of 61 surface water samples from Kentucky, USA (2020–2022), provided 61 presumed E. coli isolates, of which 28 isolates were obtained from tetracycline-treated media. Species identification and tetracycline resistance evaluation were performed. It was found that 82% of isolates were E. coli, and 18% were other species; 97% were identified as E. coli when using the API20E identification system. The MicroScan system yielded Enterobacter cloacae false positives in 20% of isolates. Adding tetracycline to ColiGlow increased the odds of isolating tetracycline-resistant E. coli 18-fold. Tetracycline-treated samples yielded 100% tetracycline-resistant E. coli when the total E. coli densities were within the enumeration range of the method. ColiGlow with tetracycline shows promise for monitoring tetracycline-resistant E. coli in natural waters and potentially aiding AMR surveillance in resource-limited settings among other environments. Full article
(This article belongs to the Special Issue Water-Borne Pathogens)
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17 pages, 9957 KiB  
Article
Evaluation of Wild Peanut Species and Their Allotetraploids for Resistance against Thrips and Thrips-Transmitted Tomato Spotted Wilt Orthotospovirus (TSWV)
by Yi-Ju Chen, Sudeep Pandey, Michael Catto, Soraya Leal-Bertioli, Mark R. Abney, Sudeep Bag, Mark Hopkins, Albert Culbreath and Rajagopalbabu Srinivasan
Pathogens 2023, 12(9), 1102; https://doi.org/10.3390/pathogens12091102 - 28 Aug 2023
Cited by 4 | Viewed by 1828
Abstract
Thrips-transmitted tomato spotted wilt orthotospovirus (TSWV) causes spotted wilt disease in peanut (Arachis hypogaea L.) and limits yield. Breeding programs have been developing TSWV-resistant cultivars, but availability of sources of resistance against TSWV in cultivated germplasm is extremely limited. Diploid wild Arachis [...] Read more.
Thrips-transmitted tomato spotted wilt orthotospovirus (TSWV) causes spotted wilt disease in peanut (Arachis hypogaea L.) and limits yield. Breeding programs have been developing TSWV-resistant cultivars, but availability of sources of resistance against TSWV in cultivated germplasm is extremely limited. Diploid wild Arachis species can serve as important sources of resistance, and despite ploidy barriers (cultivated peanut is tetraploid), their usage in breeding programs is now possible because of the knowledge and development of induced interspecific allotetraploid hybrids. This study screened 10 wild diploid Arachis and six induced allotetraploid genotypes via thrips-mediated TSWV transmission assays and thrips’ feeding assays in the greenhouse. Three parameters were evaluated: percent TSWV infection, virus accumulation, and temporal severity of thrips feeding injury. Results indicated that the diploid A. stenosperma accession V10309 and its derivative-induced allotetraploid ValSten1 had the lowest TSWV infection incidences among the evaluated genotypes. Allotetraploid BatDur1 had the lowest thrips-inflicted damage at each week post thrips release, while diploid A. batizocoi accession K9484 and A. duranensis accession V14167 had reduced feeding damage one week post thrips release, and diploids A. valida accession GK30011 and A. batizocoi had reduced feeding damage three weeks post thrips releasethan the others. Overall, plausible TSWV resistance in diploid species and their allotetraploid hybrids was characterized by reduced percent TSWV infection, virus accumulation, and feeding severity. Furthermore, a few diploids and tetraploid hybrids displayed antibiosis against thrips. These results document evidence for resistance against TSWV and thrips in wild diploid Arachis species and peanut-compatible-induced allotetraploids. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)
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14 pages, 675 KiB  
Review
Joining Forces against Antibiotic Resistance: The One Health Solution
by Eleonora Cella, Marta Giovanetti, Francesca Benedetti, Fabio Scarpa, Catherine Johnston, Alessandra Borsetti, Giancarlo Ceccarelli, Taj Azarian, Davide Zella and Massimo Ciccozzi
Pathogens 2023, 12(9), 1074; https://doi.org/10.3390/pathogens12091074 - 23 Aug 2023
Cited by 25 | Viewed by 4854
Abstract
Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle [...] Read more.
Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle complex health challenges such as antibiotic resistance. In the context of One Health, antibiotic resistance refers to the ability of bacteria to withstand the efficacy of antibiotics, rendering them less effective or completely ineffective in treating infections. The emergence and spread of antibiotic-resistant bacteria pose a threat to human and animal health, as well as to the effectiveness of medical treatments and veterinary interventions. In particular, One Health recognizes that antibiotic use in human medicine, animal agriculture, and the environment are interconnected factors contributing to the development and spread of antibiotic resistance. For example, the misuse and overuse of antibiotics in human healthcare, including inappropriate prescribing and patient non-compliance, can contribute to the selection and spread of resistant bacteria. Similarly, the use of antibiotics in livestock production for growth promotion and disease prevention can contribute to the development of antibiotic resistance in animals and subsequent transmission to humans through the food chain. Addressing antibiotic resistance requires a collaborative One Health approach that involves multiple participants, including healthcare professionals, veterinarians, researchers, and policymakers. Full article
(This article belongs to the Special Issue Reviews of Infectious Diseases)
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18 pages, 16402 KiB  
Article
Genomic and Phylogenetic Analysis of Bacillus cereus Biovar anthracis Isolated from Archival Bone Samples Reveals Earlier Natural History of the Pathogen
by Michael H. Norris, Diansy Zincke, David J. Daegling, John Krigbaum, W. Scott McGraw, Alexander Kirpich, Ted L. Hadfield and Jason K. Blackburn
Pathogens 2023, 12(8), 1065; https://doi.org/10.3390/pathogens12081065 - 20 Aug 2023
Viewed by 1738
Abstract
(1) Background: Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic [...] Read more.
(1) Background: Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic analysis found that B. cereus had acquired two anthrax-like plasmids, one a pXO1-like toxin producing plasmid and the other a pXO2-like plasmid encoding capsule. Bcbva caused animal fatalities in Cameroon, Democratic Republic of Congo, and the Central African Republic between 2004 and 2012. (2) Methods: The pathogen had acquired plasmids in the wild and that was discovered as the cause of widespread animal fatalities in the early 2000s. Primate bones had been shipped out of the endemic zone for anthropological studies prior to the realized danger of contamination with Bcbva. Spores were isolated from the bone fragments and positively identified as Bcbva. Strains were characterized by classical microbiological methods and qPCR. Four new Bcbva isolates were whole-genome sequenced. Chromosomal and plasmid phylogenomic analysis was performed to provide temporal and spatial context to these new strains and previously sequenced Bcbva. Tau and principal component analyses were utilized to identify genetic and spatial case patterns in the Taï National Park anthrax zone. (3) Results: Preliminary studies positively identified Bcbva presence in several archival bone fragments. The animals in question died between 1994 and 2010. Previously, the earliest archival strains of Bcbva were identified in 1996. Though the pathogen has a homogeneous genome, spatial analyses of a subset of mappable isolates from Taï National Park revealed strains found closer together were generally more similar, with strains from chimpanzees and duikers having the widest distribution. Ancestral strains were located mostly in the west of the park and had lower spatial clustering compared to more recent isolates, indicating a local increase in genetic diversity of Bcbva in the park over space and time. Global clustering analysis indicates patterns of genetic diversity and distance are shared between the ancestral and more recently isolated type strains. (4) Conclusions: Our strains have the potential to unveil historical genomic information not available elsewhere. This information sheds light on the evolution and emergence of a dangerous anthrax-causing pathogen. Full article
(This article belongs to the Special Issue Anthrax—a Threat beyond Bacillus anthracis)
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19 pages, 2303 KiB  
Review
Malaria Genomics, Vaccine Development, and Microbiome
by Xinzhuan Su, Rachel V. Stadler, Fangzheng Xu and Jian Wu
Pathogens 2023, 12(8), 1061; https://doi.org/10.3390/pathogens12081061 - 18 Aug 2023
Cited by 2 | Viewed by 2985
Abstract
Recent advances in malaria genetics and genomics have transformed many aspects of malaria research in areas of molecular evolution, epidemiology, transmission, host–parasite interaction, drug resistance, pathogenicity, and vaccine development. Here, in addition to introducing some background information on malaria parasite biology, parasite genetics/genomics, [...] Read more.
Recent advances in malaria genetics and genomics have transformed many aspects of malaria research in areas of molecular evolution, epidemiology, transmission, host–parasite interaction, drug resistance, pathogenicity, and vaccine development. Here, in addition to introducing some background information on malaria parasite biology, parasite genetics/genomics, and genotyping methods, we discuss some applications of genetic and genomic approaches in vaccine development and in studying interactions with microbiota. Genetic and genomic data can be used to search for novel vaccine targets, design an effective vaccine strategy, identify protective antigens in a whole-organism vaccine, and evaluate the efficacy of a vaccine. Microbiota has been shown to influence disease outcomes and vaccine efficacy; studying the effects of microbiota in pathogenicity and immunity may provide information for disease control. Malaria genetics and genomics will continue to contribute greatly to many fields of malaria research. Full article
(This article belongs to the Special Issue Models in Parasite and Pathogen Evolution)
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14 pages, 1303 KiB  
Article
Biologically Relevant Murine Models of Chronic Pseudomonas aeruginosa Respiratory Infection
by Aoife M. Rodgers, Jaime Lindsay, Avril Monahan, Alice V. Dubois, Aduragbemi A. Faniyi, Barry J. Plant, Marcus A. Mall, Miquel B. Ekkelenkamp, Stuart Elborn and Rebecca J. Ingram
Pathogens 2023, 12(8), 1053; https://doi.org/10.3390/pathogens12081053 - 17 Aug 2023
Cited by 1 | Viewed by 2071
Abstract
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have [...] Read more.
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described: a clinical isolate infection model, utilising isolates obtained from patients with CF; an incomplete antibiotic clearance model, leading to bacterial bounce-back; and the establishment of chronic infection; and an adapted water bottle chronic infection model. These models circumvent the requirement for a surgical procedure and, importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease-2nd Volume)
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13 pages, 710 KiB  
Article
Presence of Equine and Bovine Coronaviruses, Endoparasites, and Bacteria in Fecal Samples of Horses with Colic
by Moritz Stummer, Vicky Frisch, Frauke Glitz, Barbara Hinney, Joachim Spergser, Jürgen Krücken, Irina Diekmann, Katharina Dimmel, Christiane Riedel, Jessika-Maximiliane V. Cavalleri, Till Rümenapf, Anja Joachim, Manolis Lyrakis and Angelika Auer
Pathogens 2023, 12(8), 1043; https://doi.org/10.3390/pathogens12081043 - 15 Aug 2023
Viewed by 1721
Abstract
Acute abdominal pain (colic) is one of the major equine health threats worldwide and often necessitates intensive veterinary medical care and surgical intervention. Equine coronavirus (ECoV) infections can cause colic in horses but are rarely considered as a differential diagnosis. To determine the [...] Read more.
Acute abdominal pain (colic) is one of the major equine health threats worldwide and often necessitates intensive veterinary medical care and surgical intervention. Equine coronavirus (ECoV) infections can cause colic in horses but are rarely considered as a differential diagnosis. To determine the frequency of otherwise undetected ECoV infections in horses with acute colic, fresh fecal samples of 105 horses with acute colic and 36 healthy control horses were screened for viruses belonging to the Betacoronavirus 1 species by RT-PCR as well as for gastrointestinal helminths and bacteria commonly associated with colic. Horses with colic excreted significantly fewer strongyle eggs than horses without colic. The prevalence of anaerobic, spore-forming, gram-positive bacteria (Clostridium perfringens and Clostridioides difficile) was significantly higher in the feces of horses with colic. Six horses with colic (5.7%) and one horse from the control group (2.8%) tested positive for Betacoronaviruses. Coronavirus-positive samples were sequenced to classify the virus by molecular phylogeny (N gene). Interestingly, in three out of six coronavirus-positive horses with colic, sequences closely related to bovine coronaviruses (BCoV) were found. The pathogenic potential of BCoV in horses remains unclear and warrants further investigation. Full article
(This article belongs to the Special Issue Coronaviruses: Virology and Zoonotic Potential)
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23 pages, 3241 KiB  
Article
Brucella ceti Infection in Striped Dolphins from Italian Seas: Associated Lesions and Epidemiological Data
by Carla Grattarola, Antonio Petrella, Giuseppe Lucifora, Gabriella Di Francesco, Fabio Di Nocera, Antonio Pintore, Cristiano Cocumelli, Giuliana Terracciano, Antonio Battisti, Ludovica Di Renzo, Donatella Farina, Cristina Esmeralda Di Francesco, Maria Ines Crescio, Simona Zoppi, Alessandro Dondo, Barbara Iulini, Katia Varello, Walter Mignone, Maria Goria, Virginia Mattioda, Federica Giorda, Giovanni Di Guardo, Anna Janowicz, Manuela Tittarelli, Fabrizio De Massis, Cristina Casalone and Giuliano Garofoloadd Show full author list remove Hide full author list
Pathogens 2023, 12(8), 1034; https://doi.org/10.3390/pathogens12081034 - 13 Aug 2023
Cited by 5 | Viewed by 2835
Abstract
Brucella ceti infections have been increasingly reported in cetaceans. In this study, we analyzed all cases of B. ceti infection detected in striped dolphins stranded along the Italian coastline between 2012 and 2021 (N = 24). We focused on the pathogenic role [...] Read more.
Brucella ceti infections have been increasingly reported in cetaceans. In this study, we analyzed all cases of B. ceti infection detected in striped dolphins stranded along the Italian coastline between 2012 and 2021 (N = 24). We focused on the pathogenic role of B. ceti through detailed pathological studies, and ad hoc microbiological, biomolecular, and serological investigations, coupled with a comparative genomic analysis of the strains. Neurobrucellosis was observed in 20 animals. The primary histopathologic features included non-suppurative meningoencephalitis (N = 9), meningitis (N = 6), and meningoencephalomyelitis (N = 5), which was also associated with typical lesions in other tissues (N = 8). Co-infections were detected in more than half of the cases, mostly involving Cetacean Morbillivirus (CeMV). The 24 B. ceti isolates were assigned primarily to sequence type 26 (ST26) (N = 21) and, in a few cases, ST49 (N = 3). The multilocus sequence typing (cgMLST) based on whole genome sequencing (WGS) data showed that strains from Italy clustered into four genetically distinct clades. Plotting these clades onto a geographic map suggests a link between their phylogeny and the topographical distribution. These results support the role of B. ceti as a primary neurotropic pathogen for striped dolphins and highlight the utility of WGS data in understanding the evolution of this emerging pathogen. Full article
(This article belongs to the Special Issue Pathogens in 2023)
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16 pages, 2308 KiB  
Article
HLA-II-Dependent Neuroimmune Changes in Group A Streptococcal Necrotizing Fasciitis
by Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K. Combs and Suba Nookala
Pathogens 2023, 12(8), 1000; https://doi.org/10.3390/pathogens12081000 - 31 Jul 2023
Cited by 1 | Viewed by 2058
Abstract
Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis [...] Read more.
Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against peripheral GAS infections, these interactions may simultaneously trigger neuropathology and, in some cases, induce persistent alterations in the glial phenotypes. Here, we studied the consequences of peripheral GAS skin infection on the brain in an HLA-II transgenic mouse model of GAS NF with and without treatment with an antibiotic, clindamycin (CLN). Mice expressing the human HLA-II DR3 (DR3) or the HLA-II DR4 (DR4) allele were divided into three groups: (i) uninfected controls, (ii) subcutaneously infected with a clinical GAS strain isolated from a patient with GAS NF, and (iii) GAS-infected with CLN treatment (10 mg/kg/5 days, intraperitoneal). The groups were monitored for 15 days post-infection. Skin GAS burden and lesion area, splenic and hippocampal mRNA levels of inflammatory markers, and immunohistochemical changes in hippocampal GFAP and Iba-1 immunoreactivity were assessed. Skin GAS burden and hippocampal mRNA levels of the inflammatory markers S100A8/A9, IL-1β, IL-33, inflammasome-related caspase-1 (Casp1), and NLRP6 were elevated in infected DR3 but not DR4 mice. The levels of these markers were significantly reduced following CLN treatment in DR3 mice. Although GAS was not detectable in the brain, astrocyte (GFAP) and microglia (Iba-1) activation were evident from increased GFAP and Iba-1 mRNA levels in DR3 and DR4 mice. However, CLN treatment significantly reduced GFAP mRNA levels in DR3 mice, not DR4 mice. Our data suggest a skin–brain axis during GAS NF, demonstrating that peripherally induced pathological conditions regulate neuroimmune changes and gliotic events in the brain. Full article
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14 pages, 1528 KiB  
Article
Dynamics of Infections in Cattle and Rhipicephalus microplus: A Preliminary Study
by Elianne Piloto-Sardiñas, Angélique Foucault-Simonin, Alejandra Wu-Chuang, Lourdes Mateos-Hernández, Roxana Marrero-Perera, Lianet Abuin-Denis, Lisset Roblejo-Arias, Cristian Díaz-Corona, Zbigniew Zając, Joanna Kulisz, Aneta Woźniak, Sara Moutailler, Belkis Corona-González and Alejandro Cabezas-Cruz
Pathogens 2023, 12(8), 998; https://doi.org/10.3390/pathogens12080998 - 30 Jul 2023
Cited by 4 | Viewed by 1777
Abstract
Tick-borne pathogens (TBPs) pose a significant threat to livestock, including bovine species. This study aimed to investigate TBPs in cattle and ticks across four sampling points, utilizing real-time microfluidic PCR. The results revealed that Rhipicephalus microplus ticks were found infesting all animals. Among [...] Read more.
Tick-borne pathogens (TBPs) pose a significant threat to livestock, including bovine species. This study aimed to investigate TBPs in cattle and ticks across four sampling points, utilizing real-time microfluidic PCR. The results revealed that Rhipicephalus microplus ticks were found infesting all animals. Among the detected TBPs in cattle, Anaplasma marginale was the most frequently identified, often as a single infection, although mixed infections involving Rickettsia felis, uncharacterized Rickettsia sp., and Anaplasma sp. were also observed. In ticks, A. marginale was predominant, along with R. felis, Rickettsia sp., and Ehrlichia sp. It is noteworthy that although A. marginale consistently infected all cattle during various sampling times, this pathogen was not detected in all ticks. This suggests a complex dynamic of pathogen acquisition by ticks. A phylogenetic analysis focused on the identification of Anaplasma species using amplified 16S rDNA gene fragments revealed the presence of A. marginale and Anaplasma platys strains in bovines. These findings underscore the presence of multiple TBPs in both cattle and ticks, with A. marginale being the most prevalent. Understanding the dynamics and phylogenetics of TBPs is crucial for developing effective control strategies to mitigate tick-borne diseases in livestock. Full article
(This article belongs to the Collection Advances in Tick Research)
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14 pages, 3549 KiB  
Article
Genomic Analysis of Yersinia pestis Strains from Brazil: Search for Virulence Factors and Association with Epidemiological Data
by João Luiz de Lemos Padilha Pitta, Matheus Filgueira Bezerra, Diego Leandro Reis da Silva Fernandes, Tessa de Block, Ane de Souza Novaes, Alzira Maria Paiva de Almeida and Antonio Mauro Rezende
Pathogens 2023, 12(8), 991; https://doi.org/10.3390/pathogens12080991 - 28 Jul 2023
Cited by 2 | Viewed by 1872
Abstract
Yersinia pestis, the etiological agent of the plague, is considered a genetically homogeneous species. Brazil is currently in a period of epidemiological silence but plague antibodies are still detected in sentinel animals, suggesting disease activity in the sylvatic cycle. The present study [...] Read more.
Yersinia pestis, the etiological agent of the plague, is considered a genetically homogeneous species. Brazil is currently in a period of epidemiological silence but plague antibodies are still detected in sentinel animals, suggesting disease activity in the sylvatic cycle. The present study deployed an in silico approach to analyze virulence factors among 407 Brazilian genomes of Y. pestis belonging to the Fiocruz Collection (1966–1997). The pangenome analysis associated several known virulence factors of Y. pestis in clades according to the presence or absence of genes. Four main strain clades (C, E, G, and H) exhibited the absence of various virulence genes. Notably, clade G displayed the highest number of absent genes, while clade E showed a significant absence of genes related to the T6SS secretion system and clade H predominantly demonstrated the absence of plasmid-related genes. These results suggest attenuation of virulence in these strains over time. The cgMLST analysis associated genomic and epidemiological data highlighting evolutionary patterns related to the isolation years and outbreaks of Y. pestis in Brazil. Thus, the results contribute to the understanding of the genetic diversity and virulence within Y. pestis and the potential for utilizing genomic data in epidemiological investigations. Full article
(This article belongs to the Special Issue An Ancient Terror, Yersinia pestis: What's New?)
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12 pages, 1621 KiB  
Article
Trends from the Last Decade with Nontuberculous Mycobacteria Lung Disease (NTM-LD): Clinicians’ Perspectives in Regional Center of Pulmonology in Bydgoszcz, Poland
by Grzegorz Przybylski, Jakub Bukowski, Weronika Kowalska, Marta Pilaczyńska-Cemel and Dorota Krawiecka
Pathogens 2023, 12(8), 988; https://doi.org/10.3390/pathogens12080988 - 28 Jul 2023
Cited by 5 | Viewed by 1734
Abstract
Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and [...] Read more.
Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and assess the frequency and clinical relevance of isolation of NTM in the Regional Center of Pulmonology in Bydgoszcz, hospital of Northern Poland. Design: Clinical, radiological, and microbiological data were collected from all patients from whom NTM was isolated between 2013 and 2022. Data were reviewed retrospectively. Diagnostic criteria for NTM-LD published by the American Thoracic Society (ATS) were used to determine clinical relevance. Material and methods: The study comprised 81,985 clinical specimens submitted for mycobacterial culture in the Department of Microbiology at the Regional Center of Pulmonology in Bydgoszcz between 2013 and 2022. Clinical specimens were processed according to the standard procedure in mycobacteria laboratories in Poland. NTM strains were identified using analysis of mycolic acids by chromatography as well as GenoType NTM-DR, GenoType Mycobacterium AS, and GenoType Mycobacterium CM. Results: There were 395 patients with NTM strains between 2013 and 2022. Out of them, 149 cases met the diagnostic criteria of NTM-LD and were classified as definite cases. M. kansasii (n = 77) was the most common species in the group (51.68%), followed by M. avium complex (n = 46). Patients with NTM-LD were 22–88 years old (median age was 60 years). There were 81 men and 68 women. The most common symptoms were cough, hemoptysis, and fever. Radiological X-ray images were dominated by infiltrative lesions in the upper and middle lobe of the right lung with cavities; the changes were in the upper lobe of the left lung and on both sides of the chest. They were smokers in 61%. The most common concomitant diseases were chronic obstructive pulmonary disease (COPD), diabetes mellitus, pulmonary carcinoma, and human immunodeficiency virus (HIV) infection, and other immunodeficiencies. The most common treatment was isoniazid, ethambutol, rifampicin, and ofloxacin for 18 months with a minimum of 12 months of culture negativity. Conclusions: NTM-LD infections are present with other pulmonary illnesses and extrapulmonary diseases and may be connected to primary immunologic deficiencies. These diseases concern patients of all ages and have various clinical manifestations. M. kansasii and MAC are the most prevalent NTM isolates among respiratory samples in Northern Poland. In addition, an increase in MAC and a decrease in M. kansasii both in cultivation and the cause of NTM-LD were reported. Full article
(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))
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17 pages, 2077 KiB  
Article
Corynebacterium ulcerans Infections in Eurasian Beavers (Castor fiber)
by Reinhard Sting, Catharina Pölzelbauer, Tobias Eisenberg, Rebecca Bonke, Birgit Blazey, Martin Peters, Karin Riße, Andreas Sing, Anja Berger, Alexandra Dangel and Jörg Rau
Pathogens 2023, 12(8), 979; https://doi.org/10.3390/pathogens12080979 - 26 Jul 2023
Cited by 1 | Viewed by 1720
Abstract
The Eurasian beaver (Castor fiber) has been reintroduced successfully in Germany since the 1990s. Since wildlife is an important source of zoonotic infectious diseases, monitoring of invasive and reintroduced species is crucial with respect to the One Health approach. Three Eurasian beavers [...] Read more.
The Eurasian beaver (Castor fiber) has been reintroduced successfully in Germany since the 1990s. Since wildlife is an important source of zoonotic infectious diseases, monitoring of invasive and reintroduced species is crucial with respect to the One Health approach. Three Eurasian beavers were found dead in the German federal states of Bavaria, North Rhine–Westphalia and Baden–Wuerttemberg in 2015, 2021 and 2022, respectively. During post-mortem examinations, Corynebacterium (C.) ulcerans could be isolated from the abscesses of two beavers and from the lungs of one of the animals. Identification of the bacterial isolates at the species level was carried out by spectroscopic analysis using MALDI-TOF MS, FT-IR and biochemical profiles and were verified by molecular analysis based on 16-23S internal transcribed spacer (ITS) region sequencing. Molecular characterization of the C. ulcerans isolates using whole-genome sequencing (WGS) revealed a genome size of about 2.5 Mbp and a GC content of 53.4%. Multilocus sequence typing (MLST) analysis classified all three isolates as the sequence type ST-332. A minimum spanning tree (MST) based on cgMLST allelic profiles, including 1211 core genes of the sequenced C. ulcerans isolates, showed that the beaver-derived isolates clearly group on the branch of C. ulcerans with the closest relationship to each other, in close similarity to an isolate from a dog. Antibiotic susceptibility testing revealed resistance to clindamycin and, in one strain, to erythromycin according to EUCAST, while all isolates were susceptible to the other antimicrobials tested. Full article
(This article belongs to the Special Issue Emerging Zoonoses: The Bridge between Human and Animal Diseases in the One Health Paradigm)
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15 pages, 4500 KiB  
Article
Establishment of a Nipah Virus Disease Model in Hamsters, including a Comparison of Intranasal and Intraperitoneal Routes of Challenge
by Stephen Findlay-Wilson, Lucy Flett, Francisco J. Salguero, Ines Ruedas-Torres, Susan Fotheringham, Linda Easterbrook, Victoria Graham and Stuart Dowall
Pathogens 2023, 12(8), 976; https://doi.org/10.3390/pathogens12080976 - 26 Jul 2023
Cited by 2 | Viewed by 1798
Abstract
Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through [...] Read more.
Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through exposure of infected pigs, ingestion of contaminated food, or through contact with an infected person. With no approved treatments or vaccines, NiV poses a threat to human public health and has epidemic potential. To aid with the assessment of emerging interventions being developed, an expansion of preclinical testing capability is required. Given variations in the model parameters observed in different sites during establishment, optimisation of challenge routes and doses is required. Upon evaluating the hamster model, an intranasal route of challenge was compared with intraperitoneal delivery, demonstrating a more rapid dissemination to wider tissues in the latter. A dose effect was observed between those causing respiratory illness and those resulting in neurological disease. The data demonstrate the successful establishment of the hamster model of NiV disease for subsequent use in the evaluation of vaccines and antivirals. Full article
(This article belongs to the Special Issue Emerging Viruses and Viral Zoonoses)
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13 pages, 286 KiB  
Review
The Importance of the One Health Concept in Combating Zoonoses
by Elina Horefti
Pathogens 2023, 12(8), 977; https://doi.org/10.3390/pathogens12080977 - 26 Jul 2023
Cited by 9 | Viewed by 3206
Abstract
One Health fundamentally acknowledges that human health is linked to animal health and the environment. One of the pillars One Health is built on is zoonoses. Through the years, zoonotic infections have caused numerous outbreaks and pandemics, as well as millions of fatalities, [...] Read more.
One Health fundamentally acknowledges that human health is linked to animal health and the environment. One of the pillars One Health is built on is zoonoses. Through the years, zoonotic infections have caused numerous outbreaks and pandemics, as well as millions of fatalities, with the COVID-19 pandemic being the latest one. Apart from the consequences to public health, zoonoses also affect society and the economy. Since its establishment, One Health has contributed significantly to the protection of humans, animals, and the environment, through preparedness, surveillance, and mitigation of such public dangers. Full article
(This article belongs to the Special Issue One Health: New Approaches, Research and Innovation to Zoonoses)
20 pages, 1592 KiB  
Article
Assessing Onchocerca volvulus Intensity of Infection and Genetic Diversity Using Mitochondrial Genome Sequencing of Single Microfilariae Obtained before and after Ivermectin Treatment
by Shannon M. Hedtke, Young-Jun Choi, Anusha Kode, Gowtam C. Chalasani, Neha Sirwani, Stephen R. Jada, An Hotterbeekx, Michel Mandro, Joseph N. Siewe Fodjo, Glory Ngongeh Amambo, Raphael A. Abong, Samuel Wanji, Annette C. Kuesel, Robert Colebunders, Makedonka Mitreva and Warwick N. Grant
Pathogens 2023, 12(7), 971; https://doi.org/10.3390/pathogens12070971 - 24 Jul 2023
Cited by 4 | Viewed by 1935
Abstract
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi [...] Read more.
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4–5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample (n = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission. Full article
(This article belongs to the Section Parasitic Pathogens)
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22 pages, 13797 KiB  
Article
Art of the Kill: Designing and Testing Viral Inactivation Procedures for Highly Pathogenic Negative Sense RNA Viruses
by Judith Olejnik, Adam J. Hume, Stephen J. Ross, Whitney A. Scoon, Scott Seitz, Mitchell R. White, Ben Slutzky, Nadezhda E. Yun and Elke Mühlberger
Pathogens 2023, 12(7), 952; https://doi.org/10.3390/pathogens12070952 - 19 Jul 2023
Cited by 5 | Viewed by 3660
Abstract
The study of highly pathogenic viruses handled under BSL-4 conditions and classified as Select Agents frequently involves the transfer of inactivated materials to lower containment levels for downstream analyses. Adhering to Select Agent and BSL-4 safety regulations requires validation or verification of the [...] Read more.
The study of highly pathogenic viruses handled under BSL-4 conditions and classified as Select Agents frequently involves the transfer of inactivated materials to lower containment levels for downstream analyses. Adhering to Select Agent and BSL-4 safety regulations requires validation or verification of the inactivation procedures, which comes with an array of challenges for each method. This includes the use of cytotoxic reagents for chemical inactivation and defining the precise inactivation parameters for physical inactivation. Here, we provide a workflow for various inactivation methods using Ebola, Nipah, and Lassa viruses as our examples. We choose three distinct inactivation methods (TRIzol/TRIzol LS, aldehyde fixation using different fixatives, and heat) to highlight the challenges of each method and provide possible solutions. We show that, whereas published chemical inactivation methods are highly reliable, the parameters for heat inactivation must be clearly defined to ensure complete inactivation. In addition to the inactivation data, we also provide examples and templates for the documentation required for approval and use of inactivation SOPs, including an inactivation report, the procedure sections of developed SOPs, and an electronic inactivation certificate that accompanies inactivated samples. The provided information can be used as a roadmap for similar studies at high and maximum containment laboratories. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Molecular Epidemiology, Diagnostics and Management of Viral Pathogens)
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9 pages, 474 KiB  
Article
Evaluation of Lipid Profile and Intima Media Thickness in Antiretroviral-Experienced HIV-Infected Patients Treated with Protease Inhibitor-Based Regimens versus Protease Inhibitor-Sparing Regimens
by Salvatore Martini, Mariantonietta Pisaturo, Antonio Russo, Maria Grazia Palamone, Maria Teresa Russo, Verdiana Zollo, Paolo Maggi and Nicola Coppola
Pathogens 2023, 12(7), 925; https://doi.org/10.3390/pathogens12070925 - 10 Jul 2023
Cited by 4 | Viewed by 1211
Abstract
Background: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. [...] Read more.
Background: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. The aim of our study was to evaluate whether patients treated with PIs have both greater dyslipidemia and increased intima media thickness (IMT) and atheromatous plaques compared to patients treated without PIs. Materials and Methods: A total of 110 HIV-experienced patients screened with Doppler ultrasonography of the supra-aortic trunks in December 2019 were enrolled in a retrospective cross-sectional observational study. Patients were divided into two groups: 59 in the PI-based group, treated with PIs, and 51 in the PI-sparing group. In the two groups, we evaluated lipids, cardiovascular risk factors (smoking, BMI, age, hypertension), increased pathological IMT (a value > 1 mm), and possible atheromatous plaque. Results: Serum LDL (p 0.04) and percentage of patients with hypercholesterolemia (p 0.03) were higher in the PI-based than in the PI-sparing group. Doppler data showed a trend in increase of IMT > 1 in the PI-based group, which appeared statistically significant for the section of the left common carotid artery (p 0.03). However, in multivariate logistic regression models, none of the evaluated variables were significantly associated with IMT > 1. Conclusions: Our real-life data show that patients treated with PIs have a trend of developing both greater dyslipidemia and increased pathological IMT and atheromatous plaques These findings may be useful to optimize antiretrovirals for patients with cardiovascular risk factors. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: HIV and Viral Co-infections)
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20 pages, 2738 KiB  
Article
Helminths in Invasive Raccoons (Procyon lotor) from Southwest Germany
by Nico P. Reinhardt, Marion Wassermann, Jessica Härle, Thomas Romig, Lina Kurzrock, Janosch Arnold, Ernst Großmann, Ute Mackenstedt and Reinhard K. Straubinger
Pathogens 2023, 12(7), 919; https://doi.org/10.3390/pathogens12070919 - 8 Jul 2023
Cited by 4 | Viewed by 1901
Abstract
As hosts of numerous zoonotic pathogens, the role of raccoons needs to be considered in the One Health context. Raccoons progressively expand their range as invasive alien species in Europe. This study aimed to investigate the intestinal helminth fauna of raccoons in Baden-Wuerttemberg, [...] Read more.
As hosts of numerous zoonotic pathogens, the role of raccoons needs to be considered in the One Health context. Raccoons progressively expand their range as invasive alien species in Europe. This study aimed to investigate the intestinal helminth fauna of raccoons in Baden-Wuerttemberg, Germany, as no such screening had ever been conducted there. In total, we obtained 102 animals from hunters in 2019 and 2020. Intestinal helminths were retrieved using the SSCT (segmented sedimentation and counting technique) and identified morphologically and by PCR-based Sanger sequencing. Fecal samples were assessed using the ELISA PetChekTM IP assay (IDEXX, Germany) and flotation technique. The artificial digestion method was employed for analyzing muscle tissue. We detected species of four nematode genera (Baylisascaris procyonis, Toxocara canis, Capillaria spp., and Trichuris spp.), three cestode genera (Atriotaenia cf. incisa/procyonis, Taenia martis, and Mesocestoides spp.), and three trematode genera (Isthmiophora hortensis/melis, Plagiorchis muris, and Brachylaima spp.). Echinococcus spp. and Trichinella spp. were not found. The invasive behavior and synanthropic habits of raccoons may increase the infection risk with these helminths in wildlife, domestic and zoo animals, and humans by serving as a connecting link. Therefore, it is crucial to initiate additional studies assessing these risks. Full article
(This article belongs to the Special Issue Helminth Infection and Molecular Identification in Wild and Domestic Animals)
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14 pages, 1942 KiB  
Article
Role of D(−)-Lactic Acid in Prevention of Chlamydia trachomatis Infection in an In Vitro Model of HeLa Cells
by Chiara Zalambani, Nicola Rizzardi, Giacomo Marziali, Claudio Foschi, Sara Morselli, Marielle Ezekielle Djusse, Marina Naldi, Romana Fato, Natalia Calonghi and Antonella Marangoni
Pathogens 2023, 12(7), 883; https://doi.org/10.3390/pathogens12070883 - 28 Jun 2023
Cited by 4 | Viewed by 1695
Abstract
A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(−)-lactic [...] Read more.
A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(−)-lactic acid isomer are known to exert stronger protection. However, the molecular mechanisms underlying this antimicrobial action are not well understood. The aim of this study was to investigate the role of D(−)-lactic acid isomer in the prevention of C. trachomatis infection in an in vitro HeLa cell model. We selected two strains of lactobacilli belonging to different species: a vaginal isolate of Lactobacillus crispatus that releases both D(−) and L(+) isomers and a strain of Lactobacillus reuteri that produces only the L(+) isomer. Initially, we demonstrated that L. crispatus was significantly more effective than L. reuteri in reducing C. trachomatis infectivity. A different pattern of histone acetylation and lactylation was observed when HeLa cells were pretreated for 24 h with supernatants of Lactobacillus crispatus or L. reuteri, resulting in different transcription of genes such as CCND1, CDKN1A, ITAG5 and HER-1. Similarly, distinct transcription patterns were found in HeLa cells treated with 10 mM D(−)- or L(+)-lactic acid isomers. Our findings suggest that D(−) lactic acid significantly affects two non-exclusive mechanisms involved in C. trachomatis infection: regulation of the cell cycle and expression of EGFR and α5β1-integrin. Full article
(This article belongs to the Special Issue Chlamydia trachomatis: Innate Immunity, Vaccines and Behaviour)
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17 pages, 1705 KiB  
Article
Quantitative Risk Assessment of Oocyst Versus Bradyzoite Foodborne Transmission of Toxoplasma gondii in Brazil
by Sophie Zhu, Elizabeth VanWormer, Beatriz Martínez-López, Lílian Maria Garcia Bahia-Oliveira, Renato Augusto DaMatta, Pedro Souto Rodrigues and Karen Shapiro
Pathogens 2023, 12(7), 870; https://doi.org/10.3390/pathogens12070870 - 25 Jun 2023
Cited by 3 | Viewed by 1689
Abstract
Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental [...] Read more.
Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental stage of T. gondii, oocysts, is an important source of infection in Brazil; however, no studies have quantified this risk relative to other parasite stages. We developed a Bayesian quantitative risk assessment (QRA) to estimate the relative attribution of the two primary parasite stages (bradyzoite and oocyst) that can be transmitted in foods to people in Brazil. Oocyst contamination in fruits and greens contributed significantly more to overall estimated T. gondii infections than bradyzoite-contaminated foods (beef, pork, poultry). In sensitivity analysis, treatment, i.e., cooking temperature for meat and washing efficiency for produce, most strongly affected the estimated toxoplasmosis incidence rate. Due to the lack of regional food contamination prevalence data and the high level of uncertainty in many model parameters, this analysis provides an initial estimate of the relative importance of food products. Important knowledge gaps for oocyst-borne infections were identified and can drive future studies to improve risk assessments and effective policy actions to reduce human toxoplasmosis in Brazil. Full article
(This article belongs to the Special Issue Toxoplasma gondii and Food Safety)
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21 pages, 5354 KiB  
Article
Newly Designed Poxviral Promoters to Improve Immunogenicity and Efficacy of MVA-NP Candidate Vaccines against Lethal Influenza Virus Infection in Mice
by Martin C. Langenmayer, Anna-Theresa Luelf-Averhoff, Lisa Marr, Sylvia Jany, Astrid Freudenstein, Silvia Adam-Neumair, Alina Tscherne, Robert Fux, Juan J. Rojas, Andreas Blutke, Gerd Sutter and Asisa Volz
Pathogens 2023, 12(7), 867; https://doi.org/10.3390/pathogens12070867 - 23 Jun 2023
Cited by 3 | Viewed by 1656
Abstract
Influenza, a respiratory disease mainly caused by influenza A and B, viruses of the Orthomyxoviridae, is still a burden on our society’s health and economic system. Influenza A viruses (IAV) circulate in mammalian and avian populations, causing seasonal outbreaks with high numbers [...] Read more.
Influenza, a respiratory disease mainly caused by influenza A and B, viruses of the Orthomyxoviridae, is still a burden on our society’s health and economic system. Influenza A viruses (IAV) circulate in mammalian and avian populations, causing seasonal outbreaks with high numbers of cases. Due to the high variability in seasonal IAV triggered by antigenic drift, annual vaccination is necessary, highlighting the need for a more broadly protective vaccine against IAV. The safety tested Modified Vaccinia virus Ankara (MVA) is licensed as a third-generation vaccine against smallpox and serves as a potent vector system for the development of new candidate vaccines against different pathogens. Here, we generated and characterized recombinant MVA candidate vaccines that deliver the highly conserved internal nucleoprotein (NP) of IAV under the transcriptional control of five newly designed chimeric poxviral promoters to further increase the immunogenic properties of the recombinant viruses (MVA-NP). Infections of avian cell cultures with the recombinant MVA-NPs demonstrated efficient synthesis of the IAV-NP which was expressed under the control of the five new promoters. Prime-boost or single shot immunizations in C57BL/6 mice readily induced circulating serum antibodies’ binding to recombinant IAV-NP and the robust activation of IAV-NP-specific CD8+ T cell responses. Moreover, the MVA-NP candidate vaccines protected C57BL/6 mice against lethal respiratory infection with mouse-adapted IAV (A/Puerto Rico/8/1934/H1N1). Thus, further studies are warranted to evaluate the immunogenicity and efficacy of these recombinant MVA-NP vaccines in other IAV challenge models in more detail. Full article
(This article belongs to the Special Issue Animal Models for Human Viruses)
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16 pages, 2154 KiB  
Review
The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic
by Linda Petrone, Alessandro Sette, Rory D. de Vries and Delia Goletti
Pathogens 2023, 12(7), 862; https://doi.org/10.3390/pathogens12070862 - 22 Jun 2023
Cited by 15 | Viewed by 2123
Abstract
Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell [...] Read more.
Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell responses after vaccination largely mirror those of natural infection in magnitude and functional capacity, but not in breadth, as T-cells induced by vaccination exclusively target the surface spike glycoprotein. T-cell responses offer a long-lived line of defense and, unlike humoral responses, largely retain reactivity against the SARS-CoV-2 variants. Given the increasingly recognized role of T-cell responses in protection against severe COVID-19, the circulation of SARS-CoV-2 variants, and the potential implementation of novel vaccines, it becomes imperative to continuously monitor T-cell responses. In addition to “classical” T-cell assays requiring the isolation of peripheral blood mononuclear cells, simple whole-blood-based interferon-γ release assays have a potential role in routine T-cell response monitoring. These assays could be particularly useful for immunocompromised people and other clinically vulnerable populations, where interactions between cellular and humoral immunity are complex. As we continue to live alongside COVID-19, the importance of considering immunity as a whole, incorporating both humoral and cellular responses, is crucial. Full article
(This article belongs to the Collection SARS-CoV-2 Infection and COVID-19 Disease)
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19 pages, 2241 KiB  
Article
Interactions of Mycoplasma hyopneumoniae and/or Mycoplasma hyorhinis with Streptococcus suis Serotype 2 Using In Vitro Co-Infection Models with Swine Cells
by Héloïse Pageaut, Sonia Lacouture, Mélanie Lehoux, Corinne Marois-Créhan, Mariela Segura and Marcelo Gottschalk
Pathogens 2023, 12(7), 866; https://doi.org/10.3390/pathogens12070866 - 22 Jun 2023
Cited by 1 | Viewed by 2080
Abstract
Bacterial and/or viral co-infections are very common in swine production and cause severe economic losses. Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Streptococcus suis are pathogenic bacteria that may be found simultaneously in the respiratory tracts of pigs. In the present study, the interactions [...] Read more.
Bacterial and/or viral co-infections are very common in swine production and cause severe economic losses. Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Streptococcus suis are pathogenic bacteria that may be found simultaneously in the respiratory tracts of pigs. In the present study, the interactions of S. suis with epithelial and phagocytic cells in the presence or absence of a pre-infection with M. hyopneumoniae and/or M. hyorhinis were studied. Results showed relatively limited interactions between these pathogens. A previous infection with one or both mycoplasmas did not influence the adhesion or invasion properties of S. suis in epithelial cells or its resistance to phagocytosis (including intracellular survival) by macrophages and dendritic cells. The most important effect observed during the co-infection was a clear increment in toxicity for the cells. An increase in the relative expression of the pro-inflammatory cytokines IL-6 and CXCL8 was also observed; however, this was the consequence of an additive effect due to the presence of different pathogens rather than a synergic effect. It may be hypothesized that if one or both mycoplasmas are present along with S. suis in the lower respiratory tract at the same time, then increased damage to epithelial cells and phagocytes, as well as an increased release of pro-inflammatory cytokines, may eventually enhance the invasive properties of S. suis. However, more studies should be carried out to confirm this hypothesis. Full article
(This article belongs to the Special Issue The Biology of Streptococcus and Streptococcal Infection)
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21 pages, 737 KiB  
Article
Risk Factors for Hepatitis E Virus Infection and Eating Habits in Kidney Transplant Recipients
by Eva Wu, Nadine Koch, Friederike Bachmann, Marten Schulz, Evelyn Seelow, Ulrike Weber, Johannes Waiser, Fabian Halleck, Mirko Faber, Claus-Thomas Bock, Kai-Uwe Eckardt, Klemens Budde, Jörg Hofmann, Peter Nickel and Mira Choi
Pathogens 2023, 12(6), 850; https://doi.org/10.3390/pathogens12060850 - 20 Jun 2023
Viewed by 1747
Abstract
There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of [...] Read more.
There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients’ alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m2 were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E. Full article
(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infection among Humans and Animals: Epidemiology, Clinical Characteristics, Treatment and Prevention)
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21 pages, 1445 KiB  
Review
An Overview of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae), an Emerging Cause of Human Angiostrongylosis on the Indian Subcontinent
by Divakaran Pandian, Tomáš Najer and David Modrý
Pathogens 2023, 12(6), 851; https://doi.org/10.3390/pathogens12060851 - 20 Jun 2023
Cited by 5 | Viewed by 4789
Abstract
Human angiostrongylosis is an emerging zoonosis caused by the larvae of three species of metastrongyloid nematodes of the genus Angiostrongylus, with Angiostrongylus cantonensis (Chen, 1935) being dominant across the world. Its obligatory heteroxenous life cycle includes rats as definitive hosts, mollusks as intermediate [...] Read more.
Human angiostrongylosis is an emerging zoonosis caused by the larvae of three species of metastrongyloid nematodes of the genus Angiostrongylus, with Angiostrongylus cantonensis (Chen, 1935) being dominant across the world. Its obligatory heteroxenous life cycle includes rats as definitive hosts, mollusks as intermediate hosts, and amphibians and reptiles as paratenic hosts. In humans, the infection manifests as Angiostrongylus eosinophilic meningitis (AEM) or ocular form. Since there is no comprehensive study on the disease in the Indian subcontinent, our study aims at the growing incidence of angiostrongylosis in humans, alongside its clinical course and possible causes. A systematic literature search revealed 28 reports of 45 human cases from 1966 to 2022; eosinophilic meningitis accounted for 33 cases (75.5%), 12 cases were reported as ocular, 1 case was combined, and 1 case was unspecified. The presumed source of infection was reported in 5 cases only. Importantly, 22 AEM patients reported a history of eating raw monitor lizard (Varanus spp.) tissues in the past. As apex predators, monitor lizards accumulate high numbers of L3 responsible for acute illness in humans. For ocular cases, the source was not identified. Most cases were diagnosed based on nematode findings and clinical pathology (primarily eosinophilia in the cerebrospinal fluid). Only two cases were confirmed to be A. cantonensis, one by immunoblot and the other by q-PCR. Cases of angiostrongylosis have been reported in Delhi, Karnataka, Kerala, Maharashtra, Madhya Pradesh, Puducherry, Telangana, and West Bengal. With a population of more than 1.4 billion, India is one of the least studied areas for A. cantonensis. It is likely that many cases remain undetected/unreported. Since most cases have been reported from the state of Kerala, further research may focus on this region. Gastropods, amphibians, and reptiles are commonly consumed in India; however, typical preparation methods involve cooking, which kills the nematode larvae. In addition to studying rodent and mollusk hosts, monitor lizards can be used as effective sentinels. Sequence data are urgently needed to answer the question of the identity of Angiostrongylus-like metastrongylid nematodes isolated from all types of hosts. DNA-based diagnostic methods such as q-PCR and LAMP should be included in clinical diagnosis of suspected cases and in studies of genetic diversity and species identity of nematodes tentatively identified as A. cantonensis. Full article
(This article belongs to the Special Issue Rat Lungworm Disease)
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17 pages, 2003 KiB  
Article
Evaluation of the Effect of Plectranthus amboinicus L. Leaf Extracts on the Bacterial Antioxidant System and Cell Membrane Integrity of Pseudomonas aeruginosa PA01 and Staphylococcus aureus NCTC8325
by Sheeba Sawant, Timothy C. Baldwin, Oliwia Metryka and Ayesha Rahman
Pathogens 2023, 12(6), 853; https://doi.org/10.3390/pathogens12060853 - 20 Jun 2023
Cited by 1 | Viewed by 2310
Abstract
Plectranthus amboinicus (Indian borage) has been extensively studied for its medicinal properties, which can be exploited to develop new antimicrobial therapeutics. The current study investigated the effect of Plectranthus amboinicus leaf extracts on the catalase activity, reactive oxygen species, lipid peroxidation, cytoplasmic membrane [...] Read more.
Plectranthus amboinicus (Indian borage) has been extensively studied for its medicinal properties, which can be exploited to develop new antimicrobial therapeutics. The current study investigated the effect of Plectranthus amboinicus leaf extracts on the catalase activity, reactive oxygen species, lipid peroxidation, cytoplasmic membrane permeability, and efflux pump activity in S. aureus NCTC8325 and P. aeruginosa PA01. As the enzyme catalase protects bacteria against oxidative stress, disruption of its activity creates an imbalance in reactive oxygen species (ROS) levels, which subsequently oxidizes lipid chains, leading to lipid peroxidation. In addition, bacterial cell membranes are a potential target for new antibacterial agents, as efflux pump systems play a crucial role in antimicrobial resistance. Upon exposure of the microorganisms to Indian borage leaf extracts, the observed catalase activity decreased by 60% and 20% in P. aeruginosa and S. aureus, respectively. The generation of ROS can cause oxidation reactions to occur within the polyunsaturated fatty acids of the lipid membranes and induce lipid peroxidation. To investigate these phenomena, the increase in ROS activity in P. aeruginosa and S. aureus was studied using H2DCFDA, which is oxidized to 2′,7′-dichlorofluorescein (DCF) by ROS. Furthermore, the concentration of lipid peroxidation product (malondialdehyde) was assessed using the Thiobarbituric acid assay and was shown to increase by 42.4% and 42.5% in P. aeruginosa and S. aureus, respectively. The effect of the extracts on the cell membrane permeability was monitored using diSC3-5 dye and it was observed that the cell membrane permeability of P. aeruginosa increased by 58% and of S. aureus by 83%. The effect on efflux pump activity was investigated using Rhodamine-6-uptake assay, which displayed a decrease in efflux activity of 25.5% in P. aeruginosa and 24.2% in S. aureus after treatment with the extracts. This combination of different methods to study various bacterial virulence factors provides a more robust, mechanistic understanding of the effect of P. amboinicus extracts on P. aeruginosa and S. aureus. This study thus represents the first report of the assessment of the effect of Indian borage leaf extracts on bacterial antioxidant systems and bacterial cell membranes, and can facilitate the future development of bacterial resistance modifying agents derived from P. amboinicus. Full article
(This article belongs to the Special Issue Advances in Treatment of Biofilm Infections)
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23 pages, 1287 KiB  
Review
Metallic Nanoparticles and Core-Shell Nanosystems in the Treatment, Diagnosis, and Prevention of Parasitic Diseases
by Grzegorz Król, Kamila Fortunka, Michał Majchrzak, Ewelina Piktel, Paulina Paprocka, Angelika Mańkowska, Agata Lesiak, Maciej Karasiński, Agnieszka Strzelecka, Bonita Durnaś and Robert Bucki
Pathogens 2023, 12(6), 838; https://doi.org/10.3390/pathogens12060838 - 17 Jun 2023
Cited by 7 | Viewed by 2572
Abstract
The usage of nanotechnology in the fight against parasitic diseases is in the early stages of development, but it brings hopes that this new field will provide a solution to target the early stages of parasitosis, compensate for the lack of vaccines for [...] Read more.
The usage of nanotechnology in the fight against parasitic diseases is in the early stages of development, but it brings hopes that this new field will provide a solution to target the early stages of parasitosis, compensate for the lack of vaccines for most parasitic diseases, and also provide new treatment options for diseases in which parasites show increased resistance to current drugs. The huge physicochemical diversity of nanomaterials developed so far, mainly for antibacterial and anti-cancer therapies, requires additional studies to determine their antiparasitic potential. When designing metallic nanoparticles (MeNPs) and specific nanosystems, such as complexes of MeNPs, with the shell of attached drugs, several physicochemical properties need to be considered. The most important are: size, shape, surface charge, type of surfactants that control their dispersion, and shell molecules that should assure specific molecular interaction with targeted molecules of parasites’ cells. Therefore, it can be expected that the development of antiparasitic drugs using strategies provided by nanotechnology and the use of nanomaterials for diagnostic purposes will soon provide new and effective methods of antiparasitic therapy and effective diagnostic tools that will improve the prevention and reduce the morbidity and mortality caused by these diseases. Full article
(This article belongs to the Section Parasitic Pathogens)
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11 pages, 330 KiB  
Article
Small Ruminant Lentivirus Infection in Sheep and Goats in North Portugal: Seroprevalence and Risk Factors
by João Jacob-Ferreira, Ana Cláudia Coelho, Ana Grau Vila, Delia Lacasta and Hélder Quintas
Pathogens 2023, 12(6), 829; https://doi.org/10.3390/pathogens12060829 - 14 Jun 2023
Cited by 1 | Viewed by 2069
Abstract
Small ruminant lentiviruses (SRLVs) are transmitted among ovine and caprine species. This disease is a severe problem for small ruminant production, not only for animals’ well-being but also for flocks’ efficiency. The main aim of this research was to quantify the seroprevalence and [...] Read more.
Small ruminant lentiviruses (SRLVs) are transmitted among ovine and caprine species. This disease is a severe problem for small ruminant production, not only for animals’ well-being but also for flocks’ efficiency. The main aim of this research was to quantify the seroprevalence and associated risk factors for SRLV infection in the northern region of Portugal. Samples were collected from a total of 150 flocks, of which 129 (86.0%; 95% CI: 80.67%–91.33%) had at least one seropositive animal. Out of 2607 individual blood samples, 1074 (41.2%) were positive for SRLVs. Risk factors associated with SRLV infection were species (caprine), age (>2 years old), flock size (>100 animals), production system (intensive), food production system (milk), type of activity (professional), participation in livestock competitions (yes), replacement young ewe bought (yes), and natural feeding management (yes). This knowledge empowers the implementation of effective preventive measures. Overall, biosecurity measures should be promoted and implemented with the main aim of reducing viral transmission and reducing the prevalence of this disease. We recognise that government authorities should promote and audit voluntary control and eradication programs in small ruminant flocks in the region studied. Full article
(This article belongs to the Special Issue Women’s Special Issue Series: Pathogens)
19 pages, 1722 KiB  
Review
Xylem Embolism and Pathogens: Can the Vessel Anatomy of Woody Plants Contribute to X. fastidiosa Resistance?
by Giambattista Carluccio, Davide Greco, Erika Sabella, Marzia Vergine, Luigi De Bellis and Andrea Luvisi
Pathogens 2023, 12(6), 825; https://doi.org/10.3390/pathogens12060825 - 12 Jun 2023
Cited by 5 | Viewed by 2948
Abstract
The maintenance of an intact water column in the xylem lumen several meters above the ground is essential for woody plant viability. In fact, abiotic and biotic factors can lead to the formation of emboli in the xylem, interrupting sap flow and causing [...] Read more.
The maintenance of an intact water column in the xylem lumen several meters above the ground is essential for woody plant viability. In fact, abiotic and biotic factors can lead to the formation of emboli in the xylem, interrupting sap flow and causing consequences on the health status of the plant. Anyway, the tendency of plants to develop emboli depends on the intrinsic features of the xylem, while the cyto-histological structure of the xylem plays a role in resistance to vascular pathogens, as in the case of the pathogenic bacterium Xylella fastidiosa. Analysis of the scientific literature suggests that on grapevine and olive, some xylem features can determine plant tolerance to vascular pathogens. However, the same trend was not reported in citrus, indicating that X. fastidiosa interactions with host plants differ by species. Unfortunately, studies in this area are still limited, with few explaining inter-cultivar insights. Thus, in a global context seriously threatened by X. fastidiosa, a deeper understanding of the relationship between the physical and mechanical characteristics of the xylem and resistance to stresses can be useful for selecting cultivars that may be more resistant to environmental changes, such as drought and vascular pathogens, as a way to preserve agricultural productions and ecosystems. Full article
(This article belongs to the Special Issue Pathogens in 2023)
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15 pages, 1779 KiB  
Review
Recent Insights into the Role of B Cells in Chronic Hepatitis B and C Infections
by Zgjim Osmani and Andre Boonstra
Pathogens 2023, 12(6), 815; https://doi.org/10.3390/pathogens12060815 - 8 Jun 2023
Cited by 4 | Viewed by 4005
Abstract
Chronic viral hepatitis infections, caused by the hepatitis B or C virus, are a major global health problem causing an estimated one million deaths each year. Immunological studies have classically focused on T cells, while B cells have largely been neglected. Emerging evidence, [...] Read more.
Chronic viral hepatitis infections, caused by the hepatitis B or C virus, are a major global health problem causing an estimated one million deaths each year. Immunological studies have classically focused on T cells, while B cells have largely been neglected. Emerging evidence, however, highlights a role for B cells in the immunopathogenesis of chronic hepatitis B and C infections. B cell responses appear to be altered across different clinical phases of chronic HBV infection and across stages of disease in chronic HCV infection. These B cell responses show signs of a more activated state with a simultaneous enrichment of phenotypically exhausted atypical memory B cells. Despite the fact that studies show an activating B cell signature in chronic viral hepatitis infection, antibody responses to HBsAg remain impaired in chronic HBV infection, and glycoprotein E2-specific neutralizing antibody responses remain delayed in the acute phase of HCV infection. At the same time, studies have reported that a subset of HBV- and HCV-specific B cells exhibit an exhausted phenotype. This may, at least in part, explain why antibody responses in chronic HBV and HCV patients are suboptimal. Here, we summarize recent findings and discuss upcoming research questions while looking forward to how new single-cell technologies could provide novel insights into the role of B cells in chronic viral hepatitis infections. Full article
(This article belongs to the Special Issue Research on Hepatitis B Virus: Past, Present, and Future)
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12 pages, 907 KiB  
Review
Roles of FcRn in Antigen-Presenting Cells during Autoimmunity and a Clinical Evaluation of Efgartigimod as an FcRn Blocker
by Yihan Zhou and Shisong Jiang
Pathogens 2023, 12(6), 817; https://doi.org/10.3390/pathogens12060817 - 8 Jun 2023
Cited by 5 | Viewed by 3156
Abstract
The immune system is a complex network of multiple cells, tissues, and organs that protects the body against foreign pathogenic invaders. However, the immune system may mistakenly attack healthy cells and tissues due to the cross-reactivity of anti-pathogen immunity, leading to autoimmunity by [...] Read more.
The immune system is a complex network of multiple cells, tissues, and organs that protects the body against foreign pathogenic invaders. However, the immune system may mistakenly attack healthy cells and tissues due to the cross-reactivity of anti-pathogen immunity, leading to autoimmunity by autoreactive T cells and/or autoantibody-secreting B cells. Autoantibodies can accumulate, resulting in tissue or organ damage. The neonatal crystallizable fragment receptor (FcRn) is an important factor in immune regulation through controlling the trafficking and recycling of immunoglobulin G (IgG) molecules, the most abundant antibody in humoral immunity. In addition to its role in IgG trafficking and recycling, FcRn is also involved in antigen presentation, which is a crucial step in the activation of the adaptive immune response via directing the internalization and trafficking of antigen-bound IgG immune complexes into compartments of degradation and presentation in antigen-presenting cells. Efgartigimod, an FcRn inhibitor, has shown promise in reducing the levels of autoantibodies and alleviating the autoimmune severity of myasthenia gravis, primary immune thrombocytopenia, and pemphigus vulgaris/foliaceus. This article aims to provide an overview of the importance of FcRn in antigen-presenting cells and its potential as a therapeutic target in autoimmune diseases, using efgartigimod as an example. Full article
(This article belongs to the Section Immunological Responses and Immune Defense Mechanisms)
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11 pages, 2286 KiB  
Communication
Activation of Inflammasome during Bluetongue Virus Infection
by Marie Pourcelot, Rayane Amaral da Silva Moraes, Sandrine Lacour, Aurore Fablet, Grégory Caignard and Damien Vitour
Pathogens 2023, 12(6), 801; https://doi.org/10.3390/pathogens12060801 - 4 Jun 2023
Cited by 1 | Viewed by 1524
Abstract
Bluetongue virus (BTV), a double-stranded RNA virus belonging to the Sedoreoviridae family, provokes an economically important disease in ruminants. In this study, we show that the production of activated caspase-1 and interleukin 1 beta (IL-1β) is induced in BTV-infected cells. This response seems [...] Read more.
Bluetongue virus (BTV), a double-stranded RNA virus belonging to the Sedoreoviridae family, provokes an economically important disease in ruminants. In this study, we show that the production of activated caspase-1 and interleukin 1 beta (IL-1β) is induced in BTV-infected cells. This response seems to require virus replication since a UV-inactivated virus is unable to activate this pathway. In NLRP3-/- cells, BTV could not trigger further IL-1β synthesis, indicating that it occurs through NLRP3 inflammasome activation. Interestingly, we observed differential activation levels in bovine endothelial cells depending on the tissue origin. In particular, inflammasome activation was stronger in umbilical cord cells, suggesting that these cells are more prone to induce the inflammasome upon BTV infection. Finally, the strength of the inflammasome activation also depends on the BTV strain, which points to the importance of viral origin in inflammasome modulation. This work reports the crucial role of BTV in the activation of the NLRP3 inflammasome and further shows that this activation relies on BTV replication, strains, and cell types, thus providing new insights into BTV pathogenesis. Full article
(This article belongs to the Special Issue Pathogenesis of Viral Diseases)
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16 pages, 1013 KiB  
Review
Opisthorchis viverrini—Current Understanding of the Neglected Hepatobiliary Parasite
by Matthias Yi Quan Liau, En Qi Toh and Vishalkumar Girishchandra Shelat
Pathogens 2023, 12(6), 795; https://doi.org/10.3390/pathogens12060795 - 2 Jun 2023
Cited by 10 | Viewed by 2871
Abstract
Opisthorchiasis due to Opisthorchis viverrini infection continues to be a significant public healthcare concern in various subregions of Southeast Asia, particularly in Thailand, Laos, Cambodia, Myanmar, and Vietnam. The main mode of transmission is via consumption of raw or undercooked fish, which is [...] Read more.
Opisthorchiasis due to Opisthorchis viverrini infection continues to be a significant public healthcare concern in various subregions of Southeast Asia, particularly in Thailand, Laos, Cambodia, Myanmar, and Vietnam. The main mode of transmission is via consumption of raw or undercooked fish, which is deeply embedded in the culture and tradition of the people living near the Mekong River. After ingestion, the flukes migrate to the bile ducts, potentially causing many hepatobiliary complications, including cholangitis, cholecystitis, cholelithiasis, advanced periductal fibrosis and cholangiocarcinoma. Several mechanisms of opisthorchiasis-associated cholangiocarcinogenesis have been proposed and elucidated in the past decade, providing insight and potential drug targets to prevent the development of the sinister complication. The gold standard for diagnosing opisthorchiasis is still via stool microscopy, but the advent of novel serological, antigen, and molecular tests shows promise as more convenient, alternative diagnostic methods. The mainstay of treatment of opisthorchiasis is praziquantel, while treatment of opisthorchiasis-associated cholangiocarcinoma depends on its anatomic subtype and resectability. Thus far, the most successful fluke control programme is the Lawa model based in Thailand, which raised awareness, incorporated education, and frequent surveillance of intermediate hosts to reduce transmission of opisthorchiasis. Development of vaccines using tetraspanins shows promise and is currently ongoing. Full article
(This article belongs to the Special Issue Hepatobiliary and Pancreatic Infections)
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14 pages, 2438 KiB  
Article
Molecular Investigations of Two First Brucella suis Biovar 2 Infections Cases in French Dogs
by Guillaume Girault, Vitomir Djokic, Fathia Petot-Bottin, Ludivine Perrot, Bourgoin Thibaut, Hoffmann Sébastien, Acacia Ferreira Vicente, Claire Ponsart and Luca Freddi
Pathogens 2023, 12(6), 792; https://doi.org/10.3390/pathogens12060792 - 1 Jun 2023
Cited by 5 | Viewed by 2636
Abstract
Despite Brucella suis biovar 2’s (BSB2) active circulation in wildlife, no canine infections have been reported. The present paper is the first to describe two cases of BSB2 infections in French dogs. The first case occurred in 2020 and concerned a 13-year-old male [...] Read more.
Despite Brucella suis biovar 2’s (BSB2) active circulation in wildlife, no canine infections have been reported. The present paper is the first to describe two cases of BSB2 infections in French dogs. The first case occurred in 2020 and concerned a 13-year-old male neutered Border Collie with clinical signs of prostatitis. The urine culture revealed the excretion of significant levels of Brucella in the sample. The second case concerned a German Shepherd with bilateral orchitis, in which it was possible to detect Brucella colonies following neutering. HRM-PCR and classical biotyping methods classified both isolated strains as BSB2, in contrast to expected B. canis, which is usually the etiological agent of canine brucellosis in Europe. The wgSNP and MLVA analyses highlighted the genetic proximity of two isolates to BSB2 strains originating from wildlife. No pig farms were present in the proximity of either dog’s residence, ruling out potential spill over from infected pigs. Nevertheless, the dogs used to take walks in the surrounding forests, where contact with wildlife (i.e., wild boars or hares, or their excrements) was possible. These cases highlight the importance of adopting a One Health approach to control the presence of zoonotic bacteria in wild animals and avoid spillovers into domestic animals and, potentially, humans. Full article
(This article belongs to the Special Issue Molecular Epidemiology of Zoonotic Bacterial Pathogens)
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