Pathogens

13 pages, 1648 KiB

Open AccessArticle

Does the Hfq Protein Contribute to RNA Cargo Translocation into Bacterial Outer Membrane Vesicles?

by Marisela Velez and Véronique Arluison

Pathogens 2025, 14(4), 399; https://doi.org/10.3390/pathogens14040399 - 21 Apr 2025

Gram-negative bacteria release outer membrane vesicles (OMVs) that deliver various molecules, including virulence factors, to interact with their host. Recent studies have suggested that OMVs may also serve as carriers for RNAs, particularly small regulatory noncoding RNAs (sRNAs). For these RNAs to function [...] Read more.

Gram-negative bacteria release outer membrane vesicles (OMVs) that deliver various molecules, including virulence factors, to interact with their host. Recent studies have suggested that OMVs may also serve as carriers for RNAs, particularly small regulatory noncoding RNAs (sRNAs). For these RNAs to function effectively, they typically require a protein cofactor, Hfq, known as an RNA chaperone. In previous work, using molecular imaging, Circular Dichroism CD, and InfraRed FTIR spectroscopies, we demonstrated that Hfq interacts with the bacterial inner membrane and forms pores, suggesting a possible role in translocating RNA from the cytoplasm to periplasm and then to OMVs. In this study, we expand on our previous findings and provide evidence that RNA molecules bind to the Escherichia coli inner membrane in an Hfq-dependent manner. Moreover, we show that the lipid nature, in particular the presence of a cardiolipin-rich domain, is crucial for this interaction. These results reveal a new aspect of RNA translocation through the inner membrane, for further packaging in OMVs, and underscore the importance of Hfq in this mechanism. Full article

(This article belongs to the Section Bacterial Pathogens)

► Show Figures

Figure 1

21 pages, 923 KiB

Open AccessReview

Trans-Kingdom sRNA Silencing in Sclerotinia sclerotiorum for Crop Fungal Disease Management

by Yuqing Ouyang, Yunong Xia, Xianyu Tang, Lei Qin and Shitou Xia

Pathogens 2025, 14(4), 398; https://doi.org/10.3390/pathogens14040398 - 21 Apr 2025

Abstract

Sclerotinia sclerotiorum is a globally widespread and vast destructive plant pathogenic fungus that causes significant yield losses in crops. Due to the lack of effective resistant germplasm resources, the control of diseases caused by S. sclerotiorum largely relies on chemical fungicides. However, excessive [...] Read more.

Sclerotinia sclerotiorum is a globally widespread and vast destructive plant pathogenic fungus that causes significant yield losses in crops. Due to the lack of effective resistant germplasm resources, the control of diseases caused by S. sclerotiorum largely relies on chemical fungicides. However, excessive use of these chemicals not only causes environmental concerns but also leads to the increased development of resistance in S. sclerotiorum. In contrast, trans-kingdom sRNA silencing-based technologies, such as host-induced gene silencing (HIGS) and spray-induced gene silencing (SIGS), offer novel, effective, and environmentally friendly methods for the management of S. sclerotiorum infection. This review summarizes recent advances in the identification of S. sclerotiorum pathogenic genes, target gene selection, categories, and application of trans-kingdom RNA interference (RNAi) technologies targeting this pathogen. Although some challenges, including off-target effects and the efficiency of external sRNA uptake, exist, recent findings have proposed solutions for further improvement. Combined with the latest developments in CRISPR/Cas gene editing and other technologies, trans-kingdom RNAi has significant potential to become a crucial tool in the control of sclerotinia stem rot (SSR), mitigating the impact of S. sclerotiorum on crop production. Full article

(This article belongs to the Special Issue Filamentous Fungal Pathogens: 2nd Edition)

► Show Figures

Figure 1

31 pages, 398 KiB

Open AccessReview

Encephalomyocarditis Virus in Non-Domesticated Species

by Remco A. Nederlof, Bon-sang Koo, Cecilia Sierra Arqueros, Leonor Natividad Camacho Sillero, Francis Vercammen and Jaco Bakker

Pathogens 2025, 14(4), 397; https://doi.org/10.3390/pathogens14040397 - 20 Apr 2025

Abstract

Encephalomyocarditis virus (EMCV) causes sporadic and epizootic outbreaks among various domesticated and non-domesticated animal species worldwide. Although outbreaks are mostly reported in domestic pigs, mortality is reported in elephants, ungulates, nonhuman primates (NHPs), and rodents. Rats of the genus Rattus serve as primary [...] Read more.

Encephalomyocarditis virus (EMCV) causes sporadic and epizootic outbreaks among various domesticated and non-domesticated animal species worldwide. Although outbreaks are mostly reported in domestic pigs, mortality is reported in elephants, ungulates, nonhuman primates (NHPs), and rodents. Rats of the genus Rattus serve as primary reservoirs and vectors, but alternative infection routes have been proposed. Clinical disease is characterized by acute heart failure in most taxonomic groups, often culminating in rapid death. Due to the rapid progression of the disease, diagnostic confirmation is most commonly obtained postmortem. Pathological examination reveals interstitial lymphohistiocytic myocarditis and multiorgan congestion in most cases. EMCV is often demonstrated with RT-PCR or virus isolation techniques, but other methods, e.g., serology and immunohistochemistry, are available. The rapid progression of EMCV precludes effective therapeutic intervention, though agents such as interferon, verapamil, and curcumol have shown potential efficacy. Preventative strategies are crucial, emphasizing biosecurity measures to mitigate rodent contamination of feed and water. Inactivated vaccines have demonstrated protective efficacy in experimental models involving mice, pigs, and elephants, with analogous immunogenic responses observed in various zoological species. Live attenuated vaccines have conferred protection in pigs and NHPs, albeit with variable seroconversion rates in different species. Full article

(This article belongs to the Special Issue Current Challenges in Veterinary Virology)

11 pages, 1393 KiB

Open AccessCommunication

First Molecular Detection of Porcine Cytomegalovirus (PCMV) and Porcine Lymphotropic Herpesvirus (PLHV) in Domestic Pigs in Poland

by Piotr Cybulski, Wojciech Socha, Artur Jabłoński, Radosław Kondratiuk, Weronika Rybkowska, Tomasz Stadejek and Magdalena Larska

Pathogens 2025, 14(4), 396; https://doi.org/10.3390/pathogens14040396 - 18 Apr 2025

Viewed by 166

Abstract

Contrary to extensively studied porcine alphaherpesvirus (SuHV-1/PRV), betaherpesvirus (SuHV-2/PCMV) and Gammaherpesvirinae (SuHV-3/PLHV-1, SuHV-4/PLHV-2, SuHV-5/PLHV-3) infections remain unexplored in the swine population in Poland. The aim of this study was to characterise the prevalence of infections and local strains from each major herpesvirus subfamily [...] Read more.

Contrary to extensively studied porcine alphaherpesvirus (SuHV-1/PRV), betaherpesvirus (SuHV-2/PCMV) and Gammaherpesvirinae (SuHV-3/PLHV-1, SuHV-4/PLHV-2, SuHV-5/PLHV-3) infections remain unexplored in the swine population in Poland. The aim of this study was to characterise the prevalence of infections and local strains from each major herpesvirus subfamily on a large-scale weaner farm located in Poland. Nasal swabs collected from pigs at 6, 8 and 10 weeks of age were tested for the presence of herpesvirus infections using nested PCR specific to the pan-herpesvirus DNA polymerase (DPol) gene. The amplicons obtained from the positive samples were sequenced using the Sanger method. In total, 60% of the pigs were positive for herpesviruses, including 35.6% for porcine cytomegalovirus (SuHV-2/PCMV) and 24.4% for porcine lymphotropic herpesvirus type 1 (SuHV-3/PLHV-1). The infection rate was lowest in 6-week-old pigs—20% (6.7%—PCMV, 13.3%—PLHV-1) in comparison to 8-week-old—80% (53.3%—PCMV, 26.7% PLHV-1)—and 10-week-old pigs—80% (46.7%—PCMV, 33.3%—PLHV-1). No correlation between PCMV and PLHV-1 infections and coinfections with IAV, PRV1 or PRRSV was observed. Sequence analysis of both PLHV-1 and PCMV showed high genetic uniformity. Additionally, PLHV-1 isolates showed a close relationship to strains isolated from wild boar in Poland and pigs in Germany in recent years. In summary, our study confirmed the presence of both PLHV-1 and PCMV infections occurring early in piglet development, probably after passive immunity cessation. Full article

(This article belongs to the Special Issue Current Challenges in Veterinary Virology)

► Show Figures

Figure 1

15 pages, 3940 KiB

Open AccessArticle

Genomic Characterization of Potential Opportunistic Zoonotic Streptococcus parasuis Isolated in China

by Gang Liu, Yu Liu, Zhikang Jiang, Kang Liu, Xianwen Wang, Juyuan Hao, He Kong, Yajie Yu, Zicheng Ding, Min Li and Xianjie Han

Pathogens 2025, 14(4), 395; https://doi.org/10.3390/pathogens14040395 - 18 Apr 2025

Viewed by 122

Abstract

(1) Background: S. parasuis is a potential opportunistic zoonotic pathogen that can infect pigs, cattle, and humans, composed of former members of S. suis serotypes 20, 22, and 26. In recent years, unclassified serotypes and a serotype 11 S. parasuis have been discovered. [...] Read more.

(1) Background: S. parasuis is a potential opportunistic zoonotic pathogen that can infect pigs, cattle, and humans, composed of former members of S. suis serotypes 20, 22, and 26. In recent years, unclassified serotypes and a serotype 11 S. parasuis have been discovered. (2) Methods: We characterized two S. parasuis strains (FZ1 and FZ2) isolated from brain samples of paralyzed pigs and examined evolutionary divergence among 22 available S. parasuis and 8 serotype 2 S. suis genomes through whole-genome sequencing and comparative genomic analysis. We compared virulence genes (VGs) and antibiotic resistance genes (ARGs) and analyzed mobile genetic elements (MGEs) in FZ1 and FZ2. (3) Results: Comparative genomics revealed that srtC, ctpV, and sugC may represent key virulence determinants in S. parasuis, although their pathogenic potential appears attenuated compared to serotype 2 S. suis. In addition, S. parasuis exhibited primary resistance to aminoglycosides, macrolides, tetracyclines, and oxazolidinones, while demonstrating heightened susceptibility to oxazolidinone-class antibiotics. Moreover, we found an important association between MGEs and antibiotic resistance in S. parasuis FZ1 and FZ2. (4) Conclusions: This study provides new insights into the genomic and evolutionary characteristics of S. parasuis and provides a new basis for the study of bacterial pathogenesis and drug resistance in the future. Full article

► Show Figures

Figure 1

6 pages, 180 KiB

Open AccessBrief Report

Host Genetic Factors in Q Fever Susceptibility

by José-María Robaina Bordón, José-Luis Pérez-Arellano, Olga Montes-Ares, Alberto Torio-Ruiz, Michele Hernández-Cabrera, Elena Pisos-Álamo and Cristina Carranza-Rodríguez

Pathogens 2025, 14(4), 394; https://doi.org/10.3390/pathogens14040394 - 18 Apr 2025

Viewed by 148

Abstract

Several indirect findings suggest that host-related factors influence susceptibility to Coxiella burnetii infection. We decided to explore the influence of genetic factors related to both innate and adaptive immunity in acute Q fever susceptibility. TLR2 (Arg753Gln) and TLR4 (Asp299Gly, Thr399Ile) polymorphisms, along with [...] Read more.

Several indirect findings suggest that host-related factors influence susceptibility to Coxiella burnetii infection. We decided to explore the influence of genetic factors related to both innate and adaptive immunity in acute Q fever susceptibility. TLR2 (Arg753Gln) and TLR4 (Asp299Gly, Thr399Ile) polymorphisms, along with HLA-DRB1 alleles, were analyzed for 38 patients with acute Q fever, 38 matched controls, and 121 blood donors. No significant associations were found for TLR polymorphisms. However, HLA-DRB1*04 was more frequent in patients. HLA-DRB1 variants may play a role in Q fever susceptibility, supporting the need for further investigation into their potential implications for vaccination and risk assessment. Full article

19 pages, 2976 KiB

Open AccessArticle

Leptospirosis Cases During the 2024 Catastrophic Flood in Rio Grande Do Sul, Brazil

by Tani Maria Ranieri, Eduardo Viegas da Silva, Marcelo Jostmeier Vallandro, Mayara Mota de Oliveira, Regina Bones Barcellos, Roberta Vanacor Lenhardt, Loeci Natalina Timm, Aline Scarpellini Campos, Cintia Simoni, Paulo Renato da Silva Abbad, Doris Bercht Brack, Tássia Flores Rech, Juliano de Oliveira Silveira, Vivian Oliveira Estevam, Lidsy Ximenes Fonseca, Deise I. Galan and Maria Cristina Schneider

Pathogens 2025, 14(4), 393; https://doi.org/10.3390/pathogens14040393 - 17 Apr 2025

Viewed by 212

Abstract

Leptospirosis is a well-known disease that frequently occurs after floods. At the beginning of May 2024, a catastrophic flood occurred in the state of Rio Grande do Sul, Brazil, affecting two million people and leading to a state of calamity. Given the State’s [...] Read more.

Leptospirosis is a well-known disease that frequently occurs after floods. At the beginning of May 2024, a catastrophic flood occurred in the state of Rio Grande do Sul, Brazil, affecting two million people and leading to a state of calamity. Given the State’s high pre-flood leptospirosis rates, the disease became a major concern for decision-makers. This study aimed to estimate the rise in leptospirosis cases after the flood, assess the changes in case patterns before and after the disaster, and document the response of the state health surveillance center to the outbreak. We estimated the increase during the flood period (May to July 2024) by comparing it with the same period in the previous year as baseline. During the first three months of the catastrophic event, 6273 suspected cases of leptospirosis were reported to the surveillance system, and 958 cases were confirmed. The number of confirmed cases during the flood was 10.3-fold higher than the baseline. Spearman’s rank-order correlation coefficient was 0.77 (p-value < 0.0001) for the association of Health Regions regarding the rank in incidence rates of confirmed cases in the flood period and the proportion of the population with households flooded. Thirty deaths (three females) were confirmed, a 6.0-fold rise compared with 2023. The state responders carried out many activities, including epidemiological surveillance and the dissemination of information. Among the challenges faced was the lack of evidence in the literature supporting recommendations for antibiotic chemoprophylaxis for rescue personnel. Another difficulty concerned performing gold-standard laboratory diagnostic tests to confirm the enormous number of suspected cases reported during this catastrophe. Despite implementing many actions to mitigate its impact, leptospirosis remained a major challenge during the event. These findings may provide valuable insights for decision-makers facing similar situations in massive climate disasters. Full article

(This article belongs to the Special Issue One Health and Neglected Zoonotic Diseases)

► Show Figures

Figure 1

30 pages, 1300 KiB

Open AccessReview

Trypanosoma cruzi/Triatomine Interactions—A Review

by Günter A. Schaub

Pathogens 2025, 14(4), 392; https://doi.org/10.3390/pathogens14040392 - 17 Apr 2025

Viewed by 279

Abstract

This review summarizes the interactions between Trypanosoma cruzi, the etiologic agent of Chagas disease, and its vectors, the triatomines, and highlights open questions. Four important facts should be emphasized at the outset: (1) The development of T. cruzi strains and their interactions [...] Read more.

This review summarizes the interactions between Trypanosoma cruzi, the etiologic agent of Chagas disease, and its vectors, the triatomines, and highlights open questions. Four important facts should be emphasized at the outset: (1) The development of T. cruzi strains and their interactions with the mammalian host and the insect vector vary greatly. (2) Only about 10 of over 150 triatomine species have been studied for their interactions with the protozoan parasite. (3) The use of laboratory strains of triatomines makes generalizations difficult, as maintenance conditions influence the interactions. (4) The intestinal microbiota is involved in the interactions, but the mutualistic symbionts, Actinomycetales, have so far only been identified in four species of triatomines. The effects of the vector on T. cruzi are reflected in a different colonization ability of T. cruzi in different triatomine species. In addition, the conditions in the intestine lead to strong multiplication in the posterior midgut and rectum, with infectious metacyclic trypomastigotes developing almost exclusively in the latter. Starvation and feeding of the vector induce the development of certain stages of T. cruzi. The negative effects of T. cruzi on the triatomines depend on the T. cruzi strain and are particularly evident when the triatomines are stressed. The intestinal immunity of the triatomines responds to ingested blood-stage trypomastigotes of some T. cruzi strains and affects many intestinal bacteria, but not all and not the mutualistic symbionts. The specific interaction between T. cruzi and the bacteria is evident after the knockdown of antimicrobial peptides: the number of non-symbiotic bacteria increases and the number of T. cruzi decreases. In long-term infections, the suppression of intestinal immunity is indicated by the growth of specific microbiota. Full article

(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)

► Show Figures

Figure 1

19 pages, 1734 KiB

Open AccessReview

Cell Death Mechanisms in Mycobacterium abscessus Infection: A Double-Edged Sword

by Rhana Berto da Silva Prata and Roberta Olmo Pinheiro

Pathogens 2025, 14(4), 391; https://doi.org/10.3390/pathogens14040391 - 16 Apr 2025

Viewed by 255

Abstract

Infections caused by non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus, elicit diverse cell death mechanisms including apoptosis, necrosis, and pyroptosis, which play key roles in immunopathogenesis. NTM can manipulate these cell death pathways to evade host immune responses, ensuring their intracellular survival [...] Read more.

Infections caused by non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus, elicit diverse cell death mechanisms including apoptosis, necrosis, and pyroptosis, which play key roles in immunopathogenesis. NTM can manipulate these cell death pathways to evade host immune responses, ensuring their intracellular survival and persistence. Apoptosis may aid in antigen presentation and immune activation, while necrosis and pyroptosis trigger excessive inflammation, leading to tissue damage. Autophagy, a crucial cellular defense mechanism, is often induced in response to NTM infection; however, M. abscessus has evolved mechanisms to inhibit autophagic processes, enhancing its ability to survive within host cells. This manipulation of cell death pathways, particularly the dysregulation of autophagy and ferroptosis, contributes to chronic infection, immune evasion, and tissue damage, complicating disease management. Understanding these mechanisms offers potential therapeutic targets for improving treatment strategies against M. abscessus infections. Full article

(This article belongs to the Special Issue Pathogenesis and Treatment of Non-Tuberculous Mycobacterial Infections)

► Show Figures

Figure 1

13 pages, 476 KiB

Open AccessArticle

Post-Surgical Central Nervous System Infections in the Era of Multidrug Antibiotic Resistance in Greece—A Single-Center Experience of a Decade

by Konstantinos Markakis, Konstantina Kapiki, Angela Ava Arbelle Edric, Asimina Aphrodite Pappas, Georgios Feretos, Sideris Nanoudis, Dimitrios Pilalas, Theodoros Michailidis, Efthymia Protonotariou, Lemonia Skoura, Nikolaos Foroglou, Symeon Metallidis and Olga Tsachouridou

Pathogens 2025, 14(4), 390; https://doi.org/10.3390/pathogens14040390 - 16 Apr 2025

Viewed by 211

Abstract

Post-surgical central nervous system infections (PCNSIs) are a major cause of morbidity, poor functional outcomes and mortality in neurosurgical patients. These infections complicate operations of the CNS or are related to the use of neurosurgical devices or drainage catheters. Gram-negative bacteria, with multiple [...] Read more.

Post-surgical central nervous system infections (PCNSIs) are a major cause of morbidity, poor functional outcomes and mortality in neurosurgical patients. These infections complicate operations of the CNS or are related to the use of neurosurgical devices or drainage catheters. Gram-negative bacteria, with multiple resistance patterns, are often isolated and these infections are difficult to treat, due to suboptimal antibiotic therapeutic levels in the cerebrospinal fluid (CSF). This is a retrospective study of PCNSIs between 2014 and 2024 in a single center of a tertiary hospital in Thessaloniki, Greece. Out of 2401 neurosurgical procedures, forty-one were complicated by PCNSIs, yielding a total PCNSI prevalence of 1.7%. Thirty-five involved cases with positive CSF culture. The most common interventions were craniotomies for the resection of tumors or other lesions (30.1%). Most cases referred to an EVD infection. Acinetobacter baumannii was the most commonly isolated pathogen (34.1%), followed by coagulase-negative Staphylococcus (22%) and Pseudomonas spp. (14.6%). Colistin and tigecycline were the most prescribed combination regimens. The median time to the first positive CSF culture postoperatively was 11 days (IQR 18 days). Empirical antibiotic treatment was adequate in 26 (63.4%) cases. The mortality rate among these patients was 65.7%. Survivors were significantly younger than non-survivors (p < 0.01) and had a shorter ICU length of stay (p < 0.01). The type of infection, time to infection onset, isolated pathogen, susceptibility to the empirical treatment and Charlson Comorbidity Index did not differ between the two groups. The mortality rate remains high in patients with PCNSIs. An integrated approach including surgical source control, supportive care, combination antimicrobial therapy and subsequent rehabilitation are mandatory to achieve treatment success and neurological convalescence. Full article

(This article belongs to the Special Issue Hospital-Acquired Infections and Multidrug-Resistant (MDR) Pathogens)

► Show Figures

Figure 1

12 pages, 586 KiB

Open AccessArticle

HTLV-1 and Pregnancy: A Retrospective Study of Maternal and Neonatal Health Outcomes in an Endemic Region of Brazil

by Jacielma de Oliveira Freire, Maria Aparecida Figueredo Rodrigues, Greice Carolina Santos da Silva, Hugo Saba Pereira Cardoso, Marcio Luis Valença Araújo, Aloísio Santos Nascimento Filho, Briena Rodrigues Santos, Maria da Conceição Chagas de Almeida, Bernardo Galvão-Castro and Maria Fernanda Rios Grassi

Pathogens 2025, 14(4), 389; https://doi.org/10.3390/pathogens14040389 - 16 Apr 2025

Viewed by 235

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) infection poses significant challenges to maternal and neonatal health, particularly in endemic regions. Vertical transmission, which occurs most commonly through prolonged breastfeeding and rarely during pregnancy, or childbirth, perpetuates the virus within families. This observational, retrospective [...] Read more.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection poses significant challenges to maternal and neonatal health, particularly in endemic regions. Vertical transmission, which occurs most commonly through prolonged breastfeeding and rarely during pregnancy, or childbirth, perpetuates the virus within families. This observational, retrospective study analyzed HTLV-1-infected and uninfected pregnant women admitted for delivery at a university maternity hospital in Salvador, Brazil (2020–2022). Medical records provided sociodemographic, clinical, and laboratory data. The HTLV-1 infection rate was 4.61 per 1000 deliveries. The sociodemographic characteristics were similar between infected (n = 17) and uninfected (n = 34) women. HTLV-1-positive women had higher rates of unplanned and undesired pregnancies. Adverse pregnancy outcomes were frequent in both groups (94.1% vs. 91.2%), but metabolic disorders and hypertension/eclampsia were more common among the infected women. Preterm birth and postpartum complications were also more frequent (17.6% vs. 5.9%, respectively), although the difference was not statistically significant. Breastfeeding initiation within the first hours of life was lower among exposed newborns (28.6% vs. 70%; p = 0.013). Neonatal characteristics did not differ significantly between the groups. These findings highlight critical gaps in reproductive health awareness and barriers to accessing preventive interventions. Further research on therapeutic strategies is urgently needed to support the World Health Organization’s (WHO) goal of eliminating HTLV-1 vertical transmission by 2030. Full article

(This article belongs to the Section Epidemiology of Infectious Diseases)

► Show Figures

Figure 1

16 pages, 1234 KiB

Open AccessArticle

Antiviral Effect of Erdosteine in Cells Infected with Human Respiratory Viruses

by Pierachille Santus, Sergio Strizzi, Fiammetta Danzo, Mara Biasin, Irma Saulle, Claudia Vanetti, Marina Saad, Dejan Radovanovic and Daria Trabattoni

Pathogens 2025, 14(4), 388; https://doi.org/10.3390/pathogens14040388 - 15 Apr 2025

Viewed by 184

Abstract

Respiratory viral infections trigger immune and inflammatory responses that can be associated with excessive oxidative stress, glutathione (GSH) depletion, and a cytokine storm that drives virus-induced cell/tissue damage and severe disease. Erdosteine is a thiol-based drug with proven mucolytic, anti-inflammatory, antioxidant, and antibacterial [...] Read more.

Respiratory viral infections trigger immune and inflammatory responses that can be associated with excessive oxidative stress, glutathione (GSH) depletion, and a cytokine storm that drives virus-induced cell/tissue damage and severe disease. Erdosteine is a thiol-based drug with proven mucolytic, anti-inflammatory, antioxidant, and antibacterial properties, but less is known about its antiviral effects. We performed in vitro studies to investigate the antiviral and anti-inflammatory activity of erdosteine in A549-hACE2 human lung epithelial cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) and in Caco-2 human colon carcinoma cells infected with influenza A virus (H1N1). The cells were treated with different concentrations of erdosteine or its active metabolite 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MET-1) before and after viral infection. The viral replication/load in the cell culture supernatants was measured by real-time quantitative polymerase chain reaction (RT-qPCR) assay and digital droplet PCR. The gene expression of innate immune response signaling pathways and oxidative stress was analyzed by reverse transcription PCR custom-array. The results showed that erdosteine and its active metabolite, at concentrations consistent with an approved therapeutic human dosage, were not directly cytotoxic and had significant antiviral effects in cells pre-infected with SARS-CoV-2, RSV, and H1N1. The transcriptome analysis showed that erdosteine activated innate immune responses by stimulating overexpression of type I interferon and inflammasome pathways and modulated oxidative stress by inducing the modulation of oxidative stress and GSH pathways. These findings suggest that erdosteine may be a useful treatment for respiratory viral infections. Full article

(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)

► Show Figures

Figure 1

25 pages, 1368 KiB

Open AccessArticle

Mutational Analysis of Colistin-Resistant Pseudomonas aeruginosa Isolates: From Genomic Background to Antibiotic Resistance

by Telma De Sousa, Hsin-Yao Wang, Ting-Wei Lin, Manuela Caniça, Miguel J. N. Ramos, Daniela Santos, Catarina Silva, Sónia Saraiva, Racha Beyrouthy, Richard Bonnet, Michel Hébraud, Gilberto Igrejas and Patrícia Poeta

Pathogens 2025, 14(4), 387; https://doi.org/10.3390/pathogens14040387 - 15 Apr 2025

Viewed by 166

Abstract

This study analyzed eleven isolates of colistin-resistant Pseudomonas aeruginosa, originating from Portugal and Taiwan, which are associated with various pathologies. The results revealed significant genetic diversity among the isolates, with each exhibiting a distinct genetic profile. A prevalence of sequence type ST235 [...] Read more.

This study analyzed eleven isolates of colistin-resistant Pseudomonas aeruginosa, originating from Portugal and Taiwan, which are associated with various pathologies. The results revealed significant genetic diversity among the isolates, with each exhibiting a distinct genetic profile. A prevalence of sequence type ST235 was observed, characterizing it as a high-risk clone, and serotyping indicated a predominance of type O11, associated with chronic respiratory infections in cystic fibrosis (CF) patients. The phylogenetic analysis demonstrated genetic diversity among the isolates, with distinct clades and complex evolutionary relationships. Additionally, transposable elements such as Tn3 and IS6 were identified in all isolates, highlighting their importance in the mobility of antibiotic resistance genes. An analysis of antimicrobial resistance profiles revealed pan-drug resistance in all isolates, with a high prevalence of genes conferring resistance to β-lactams and aminoglycosides. Furthermore, additional analyses revealed mutations in regulatory networks and specific loci previously implicated in colistin resistance, such as pmrA, cprS, phoO, and others, suggesting a possible contribution to the observed resistant phenotype. This study has a strong impact because it not only reveals the genetic diversity and resistance mechanisms in P. aeruginosa but also identifies mutations in regulatory genes associated with colistin resistance. Full article

(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)

► Show Figures

Figure 1

33 pages, 1065 KiB

Open AccessReview

Disarming Staphylococcus aureus: Review of Strategies Combating This Resilient Pathogen by Targeting Its Virulence

by Abdelaziz Touati, Nasir Adam Ibrahim and Takfarinas Idres

Pathogens 2025, 14(4), 386; https://doi.org/10.3390/pathogens14040386 - 15 Apr 2025

Viewed by 354

Abstract

Staphylococcus aureus is a formidable pathogen notorious for its antibiotic resistance and diverse virulence mechanisms, including toxin production, biofilm formation, and immune evasion. This article explores innovative anti-virulence strategies to disarm S. aureus by targeting critical virulence factors without exerting bactericidal pressure. Key [...] Read more.

Staphylococcus aureus is a formidable pathogen notorious for its antibiotic resistance and diverse virulence mechanisms, including toxin production, biofilm formation, and immune evasion. This article explores innovative anti-virulence strategies to disarm S. aureus by targeting critical virulence factors without exerting bactericidal pressure. Key approaches include inhibiting adhesion and biofilm formation, neutralizing toxins, disrupting quorum sensing (e.g., Agr system inhibitors), and blocking iron acquisition pathways. Additionally, interventions targeting two-component regulatory systems are highlighted. While promising, challenges such as strain variability, biofilm resilience, pharmacokinetic limitations, and resistance evolution underscore the need for combination therapies and advanced formulations. Integrating anti-virulence strategies with traditional antibiotics and host-directed therapies offers a sustainable solution to combat multidrug-resistant S. aureus, particularly methicillin-resistant strains (MRSA), and mitigate the global public health crisis. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

► Show Figures

Figure 1

13 pages, 1499 KiB

Open AccessArticle

Investigating Correlation Between Gut Microbiota and Rheumatoid Arthritis Subtypes by Mendelian Randomization

by Jiaqi Wu, Yao Peng, Ruimin Tian, Hao Yu, Huating Hu, Qingchun Huang, Youhua Xu, Liang Liu and Hudan Pan

Pathogens 2025, 14(4), 385; https://doi.org/10.3390/pathogens14040385 - 15 Apr 2025

Viewed by 203

Abstract

Background: Previous studies have demonstrated that the gut microbiota (GM) and rheumatoid arthritis (RA) are significantly associated, but the causal relationship has not been fully elucidated. Methods: We investigated the association between GM and RA using Mendelian randomization (MR) with two [...] Read more.

Background: Previous studies have demonstrated that the gut microbiota (GM) and rheumatoid arthritis (RA) are significantly associated, but the causal relationship has not been fully elucidated. Methods: We investigated the association between GM and RA using Mendelian randomization (MR) with two independent samples. Our study aimed to determine the causal relationship between gut microbiota and RA, including its seronegative and seropositive subtypes. Using data from a genome-wide association study (GWAS), we identified instrumental variables for 211 gut bacteria types. We then analyzed the FinnGen GWAS dataset, which included 3877 seronegative RA cases and 285,035 controls, along with 4290 seropositive RA cases and 368,362 controls, employing the inverse variance weighted (IVW) method and rigorous tests for pleiotropy and heterogeneity to ensure reliability. Results: The IVW results revealed that Prevotella 9, Sutterella, and Christensenellaceae R.7 exhibited an adverse correlation with seronegative RA (p < 0.05). Additionally, Lachnospira, Slackia, Roseburia, Barnesiella, and Prevotella 7 were associated with a reduced occurrence of seropositive RA (p < 0.05). Conversely, Ruminococcaceae UCG002 and Ruminococcus gauvreauii were linked to an increased susceptibility to seropositive RA (p < 0.05). Notably, no significant heterogeneity (p > 0.05) or pleiotropy (p > 0.05) was detected in the analysis of the significant MR estimates. Conclusions: Our study suggested significant associations between several gut bacteria and RA subtypes, indicating a potential microbial influence on RA development. These findings enhance our understanding of the gut-joint axis in RA and highlight promising targets for future microbiota-based therapies. Full article

► Show Figures

Figure 1

8 pages, 703 KiB

Open AccessCommunication

Caffeic Acid Phenethyl Ester (CAPE) Inhibits Arginase Activity and Growth of Leishmania amazonensis Promastigotes and Intracellular Amastigotes

by Edson Roberto da Silva, André Mesquita and Claudia do Carmo Maquiaveli

Pathogens 2025, 14(4), 384; https://doi.org/10.3390/pathogens14040384 - 15 Apr 2025

Viewed by 181

Abstract

Caffeic acid phenethyl ester (CAPE) is a polyphenol produced by many plants and is found in red and green propolis. Here, we evaluated the antileishmanial activity of this natural product against Leishmania amazonensis. CAPE exhibited IC₅₀ values of 8.07 µM (95% [...] Read more.

Caffeic acid phenethyl ester (CAPE) is a polyphenol produced by many plants and is found in red and green propolis. Here, we evaluated the antileishmanial activity of this natural product against Leishmania amazonensis. CAPE exhibited IC₅₀ values of 8.07 µM (95% CI, 6.79–9.62 µM) and 13.51 µM (95% CI, 10.71–17.16 µM) against L. amazonensis promastigotes and intracellular amastigotes, respectively. Additionally, CAPE inhibited L. amazonensis arginase in a non-competitive manner with a K_i value of 1.51 ± 0.04 µM. These results highlight the potential of CAPE as a promising lead compound for developing new therapies against leishmaniasis. Full article

(This article belongs to the Special Issue New Advances in Antiparasitic Drug Development: Targets, Strategies, and Challenges)

► Show Figures

Figure 1

15 pages, 2569 KiB

Open AccessArticle

Chemical Composition, Antifungal Activity, and Plant-Protective Potential of Rosa damascena Mill. Essential Oil Against Fusarium graminearum

by Esma Özsoy, Timur Hakan Barak, Emre Yörük, Hüseyin Servi and Tapani Yli-Mattila

Pathogens 2025, 14(4), 383; https://doi.org/10.3390/pathogens14040383 - 15 Apr 2025

Viewed by 253

Abstract

Fusarium graminearum is a common plant pathogen among cereals worldwide. The application of chemical antifungal compounds is the most frequently used method in controlling F. graminearum. However, its excessive use and the genomic plasticity of the fungal genome lead to increased resistance [...] Read more.

Fusarium graminearum is a common plant pathogen among cereals worldwide. The application of chemical antifungal compounds is the most frequently used method in controlling F. graminearum. However, its excessive use and the genomic plasticity of the fungal genome lead to increased resistance levels to these chemical antifungal compounds. In this context, plant-derived compounds might play a role in protecting against Fusarium head blight (FHB) and crown rot (CR) as an alternative. In this study, we aimed to examine the antifungal effects of an essential oil obtained from Rosa damascena Mill. on the plant pathogen F. graminearum using molecular and analytical methods. The chemical composition of the essential oil was determined by GC-MS. The half effective concentration (EC₅₀) value of R. damascena essential oil (REO) for F. graminearum was determined as 604.25 µg mL⁻¹. Water-soluble tetrazolium 1 (WST-1) analyses revealed that REO caused cytotoxicity in F. graminearum. The potential oxidative stress and autophagic cell death capacity of REO towards F. graminearum was revealed via gene expression analysis and fluorescence microscopy. It was also revealed that, due to the plant-protective effect of REO, the disease severity of treated plants decreased by up to 27.78% in juvenile wheat seedlings infected by F. graminearum. Our data show that R. damascena essential oil might be used as an alternative natural ingredient in the field of plant protection. Full article

(This article belongs to the Special Issue Current Research in the Control of Plant Pathogenic Fusarium Species)

► Show Figures

Figure 1

11 pages, 2308 KiB

Open AccessArticle

First Record of Leishmania (Viannia) sp. and High Prevalence of Anaplasma marginale and Trypanosoma theileri in Zebu Cattle from Zenú Communities in Northern Colombia

by Daniel Guzmán-Vásquez, Lucas Lisboa Nunes Bonifácio, Kamila Gaudêncio da Silva Sales, Rafaela Lira Nogueira de Luna, Luis Enrique Paternina Tuiran and Filipe Dantas-Torres

Pathogens 2025, 14(4), 382; https://doi.org/10.3390/pathogens14040382 - 15 Apr 2025

Viewed by 231

Abstract

Colombia has the fourth largest livestock herd on the American continent. Cattle farms are expanding in Colombia, sometimes impacting traditional communities and reserves. This is especially true for the Zenú ethnic group, whose ancestral territory includes the valleys of the Sinú and San [...] Read more.

Colombia has the fourth largest livestock herd on the American continent. Cattle farms are expanding in Colombia, sometimes impacting traditional communities and reserves. This is especially true for the Zenú ethnic group, whose ancestral territory includes the valleys of the Sinú and San Jorge rivers, as well as the Caribbean coast around the Gulf of Morrosquillo, in the departments of Córdoba and Sucre. The present study examined the prevalence of trypanosomatids and Anaplasma spp. in zebu cattle grazing in seven Zenú communities in the Sucre department. Of the 110 cattle sampled, 56 (50.9%) tested positive for trypanosomatids. Forty 18S rRNA gene sequences generated showed >99% identity with Trypanosoma theileri, while one sequence demonstrated 99.6% identity with Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis; sequencing of the remaining 15 positive samples was unsuccessful. Regarding Anaplasma spp., 96 (87.3%) samples were positive, and the 14 msp4 gene sequences generated displayed >99% identity with Anaplasma marginale. Thus, T. theileri and A. marginale were prevalent in cattle from all Zenú communities, while Leishmania (Viannia) sp. was found in a cow from the community of La Gallera. Our findings indicate that these agents are common in zebu cattle from Zenú communities, underscoring the need for preventive measures to reduce the infection burden and potential implications for cattle production in these areas. Full article

(This article belongs to the Special Issue Vector Control and Parasitic Infection in Animals)

► Show Figures

Figure 1

16 pages, 3272 KiB

Open AccessArticle

Blood Transcriptome Profiling Highlights the Role of Intestinal Bacterial Translocation in Severe COVID-19

by Dimitrios Christos Tremoulis, Gethsimani Papadopoulou, Vasiliki Pogka, Aikaterini Argyraki, Giota Lourida, Andreas Mentis and Timokratis Karamitros

Pathogens 2025, 14(4), 381; https://doi.org/10.3390/pathogens14040381 - 14 Apr 2025

Viewed by 254

Abstract

COVID-19 has caused millions of deaths globally; however, the characterization of molecular biomarkers of severe disease remains of great scientific importance. The aim of this study was to capture the transcriptional differences of the whole blood gene expression between COVID-19 patients with mild [...] Read more.

COVID-19 has caused millions of deaths globally; however, the characterization of molecular biomarkers of severe disease remains of great scientific importance. The aim of this study was to capture the transcriptional differences of the whole blood gene expression between COVID-19 patients with mild and severe disease, using Next Generation Sequencing technologies, on admission and after 7 days. The genes which were differentially expressed in severe compared to mild patients were used for Gene Ontology (GO) enrichment analysis. Gene expression data were used to estimate the cell abundance of 22 immune cell types via digital cytometry. GO terms related to the response to molecules of bacterial origin, such as intestine-derived lipopolysaccharide (LPS), were enriched, among other dysregulated pathways, which are well described as paramount mechanisms of severe manifestations of COVID-19. The neutrophil population increased in patients with severe disease, whereas the monocyte, CD8⁺ T cell, and activated Natural Killer (NK) cell populations were depleted. These cell population dynamics are also indicative of severe COVID-19 and intestinal bacterial translocation. This study elucidates the molecular basis of severe COVID-19 and highlights intestinal bacterial translocation as a potential driver of severe disease. Full article

(This article belongs to the Section Viral Pathogens)

► Show Figures

Figure 1

17 pages, 2130 KiB

Open AccessArticle

Genotype I Newcastle Disease Virus, Isolated from Wild Duck, Can Protect Chickens Against Newcastle Disease Caused by Genotype VII

by Elizaveta Boravleva, Anastasia Treshchalina, Daria Gordeeva, Alexandra Gambaryan, Alla Belyakova, Irina Gafarova, Alexey Prilipov, Galina Sadykova, Simone Adams, Tatiana Timofeeva and Natalia Lomakina

Pathogens 2025, 14(4), 380; https://doi.org/10.3390/pathogens14040380 - 14 Apr 2025

Viewed by 207

Abstract

Newcastle disease viruses (NDVs) circulating among wild birds and poultry may differ in virulence. Some NDVs cause devastating outbreaks in chickens. The NDV/duck/Moscow/3639/2008 (d3639) strain was isolated from a wild duck. Its genome was sequenced (PP795281, GenBank) and the biological properties, specifically for [...] Read more.

Newcastle disease viruses (NDVs) circulating among wild birds and poultry may differ in virulence. Some NDVs cause devastating outbreaks in chickens. The NDV/duck/Moscow/3639/2008 (d3639) strain was isolated from a wild duck. Its genome was sequenced (PP795281, GenBank) and the biological properties, specifically for infection in chicken and mice, were studied. Strain d3639 of genotype I.2 has an F protein cleavage site (112-GKQGRL-117) and a HN protein length (616 a.a.) of the lentogenic pathotype. It was tested, in comparison with the genotype II LaSota vaccine strain, for its immunogenicity and protective efficacy against a challenge with the velogenic NDV strain NDV/chicken/Moscow/6081/2022 (ch6081) of sub-genotype VII.1.1, the complete genome of which was also sequenced in this study (PP766718, GenBank). Both the d3639 and LaSota viruses did not induce clinical signs in chickens or mice. Single immunization was performed by inoculation through drinking water with the live virus. Inoculation protected the chickens during a subsequent challenge with velogenic ch6081 and significantly reduced shedding in feces. Double immunization was sufficient to achieve prolonged immunity and prevented the shedding of the velogenic virus after the challenge. Thus, this natural lentogenic d3639 virus possesses properties similar to the LaSota vaccine strain and can protect against sub-genotype VII.1.1 NDV. Full article

(This article belongs to the Section Viral Pathogens)

► Show Figures

Figure 1

32 pages, 2927 KiB

Open AccessReview

Two Decades of Melioidosis in India: A Comprehensive Epidemiological Review

by Sriram Kannan, Suchita Singh, Venkat Abhiram Earny, Soumi Chowdhury, Mohammed Ashiq, Vandana Kalwaje Eshwara, Chiranjay Mukhopadhyay and Harpreet Kaur

Pathogens 2025, 14(4), 379; https://doi.org/10.3390/pathogens14040379 - 14 Apr 2025

Viewed by 237

Abstract

Melioidosis, caused by Burkholderia pseudomallei, is a potentially fatal infection, particularly affecting individuals with chronic conditions such as diabetes or kidney or liver diseases. This review examines melioidosis in India over the past two decades, focusing on its prevalence, risk factors and [...] Read more.

Melioidosis, caused by Burkholderia pseudomallei, is a potentially fatal infection, particularly affecting individuals with chronic conditions such as diabetes or kidney or liver diseases. This review examines melioidosis in India over the past two decades, focusing on its prevalence, risk factors and clinical manifestations. A PubMed search (2000–2024) identified a rise in melioidosis publications, with most from Southern India, followed by Eastern India, and an increase post-2019. Eight studies from 2010–2022 identified fever (86%), cough (26%) and joint pain (23%) as the most common symptoms, while diabetes (75%), alcohol abuse (19%) and cancer (6%) were primary predisposing factors. Severe clinical manifestations were also observed, including bacteremia (50%), pneumonia (37%) and splenic abscess (18%). Although environmental exposure risks were not significantly high, individuals with diabetes or chronic kidney disease, particularly those working in high-risk environments, were more likely to contract melioidosis. Cryptic environmental factors that might bridge known epidemiological risk factors are also addressed. The review emphasizes the increasing awareness and research in clinical epidemiology and also highlights a gap in studies on antimicrobial treatments, vaccines and environmental surveillance. Targeted interventions in diabetes and poverty hotspots could help control the disease more effectively. Full article

(This article belongs to the Special Issue Updates on Human Melioidosis)

► Show Figures

Figure 1

24 pages, 4413 KiB

Open AccessArticle

Mentha piperita Supplementation Promotes Growth, Immunity, and Disease Resistance in Nile tilapia Against Aeromonas hydrophila

by Attia A. Abou Zaid, Nagwa H. Mohammed, Ahmed E. Elshafey, Ebtehal E. Hussein, Adel M. El-Gamal and Haitham G. Abo-Al-Ela

Pathogens 2025, 14(4), 378; https://doi.org/10.3390/pathogens14040378 - 12 Apr 2025

Viewed by 391

Abstract

This study investigated the effects of dietary supplementation with Mentha piperita (MP) on growth, immune enhancement, and disease resistance in Nile tilapia (Oreochromis niloticus) over a 90-day period, particularly against Aeromonas hydrophila. MP was incorporated into the diets at concentrations [...] Read more.

This study investigated the effects of dietary supplementation with Mentha piperita (MP) on growth, immune enhancement, and disease resistance in Nile tilapia (Oreochromis niloticus) over a 90-day period, particularly against Aeromonas hydrophila. MP was incorporated into the diets at concentrations of 0.0%, 0.2%, 0.4%, and 0.6%. Analysis of the essential oil composition of MP identified menthol derivatives as the primary components, along with other bioactive compounds. The results revealed that MP supplementation significantly enhanced growth performance, with fish receiving the 0.6% MP diet achieving the highest weight gain, growth rate, and feed efficiency. Additionally, MP significantly enhanced the fish’s resistance to A. hydrophila infection, with the highest survival rate observed in the 0.6% MP group. Further analyses revealed that MP positively influenced blood parameters, improving RBC and WBC counts, hemoglobin levels, as well as serum immunoglobulin M and phagocytic activity. MP also mitigated oxidative stress by increasing antioxidant enzyme activity and reducing malondialdehyde levels. Moreover, MP supplementation at the concentration of 0.6% maintained intestinal integrity against bacterial damage. Gene expression analysis showed that MP upregulated insulin-like growth factor 1, suggesting a potential mechanism for improved growth. Interestingly, MP downregulated the expression of the inflammatory gene nuclear factor kappa B before the bacterial challenge, while its expression remained more downregulated post-challenge compared to control. These findings highlight the potential of MP as an effective feed additive that enhances growth rates in Nile tilapia, boosts immunity against diseases, and improves their overall health. Full article

► Show Figures

Figure 1

17 pages, 23961 KiB

Open AccessArticle

First Detection of Bluetongue Virus Type 3 in Poland in 2024—A Case Study in European Bison (Bison bonasus)

by Magdalena Larska, Anna Orłowska, Wojciech Łopuszyński, Łukasz Skurka, Agnieszka Nowakowska, Paweł Trębas, Michał K. Krzysiak, Jerzy Rola and Marcin Smreczak

Pathogens 2025, 14(4), 377; https://doi.org/10.3390/pathogens14040377 - 12 Apr 2025

Viewed by 417

Abstract

Since the emergence of serotype BTV-3, another bluetongue virus, in fall 2023, this variant has been causing great losses in livestock farming in Europe. The virus spreads faster than the epidemic BTV-8, which appeared on the continent nine years earlier. This study describes [...] Read more.

Since the emergence of serotype BTV-3, another bluetongue virus, in fall 2023, this variant has been causing great losses in livestock farming in Europe. The virus spreads faster than the epidemic BTV-8, which appeared on the continent nine years earlier. This study describes the first case of BTV-3 in Poland detected in a European bison (Bison bonasus) in Poland’s Wolin National Park, approximately 15 km from the German–Polish border. The animal suffered from a severe and fatal hemorrhagic disease. The symptoms included respiratory problems, bloody diarrhea, and rapidly progressive cachexia. In addition to the virus’s confirmation as BTV-3 and the presence of the infecting agent in the blood and spleen of the animal, the virus was also detected in one pool of blood-fed Culicoides punctatus caught near the bison enclosure two weeks after the death of the bison. This is the first detection of BTV-3 in C. punctatus, which suggests vector competency for this serotype. Phylogenetic analysis based on segment 2 of the virus revealed the homology of the Polish isolate to the BTV-3 strains circulating in the Netherlands, Germany, and Portugal, and slightly lower similarity to the BTV-3 strains detected in sheep in Sardinia (Italy) in 2018 and in Tunisia in November 2016. A retrospective serosurvey of the exposure to BTV in thirteen other European bison populations distributed over the country indicated that the observed case at the Wolin National Park was the first BTV-3 to be detected in Poland. Full article

► Show Figures

Figure 1

13 pages, 1298 KiB

Open AccessArticle

Pulmonary Manifestations of Babesiosis and Predictors of Mortality from a Quaternary Care Center in Westchester, New York

by George Williams, Luis Tatem, Kuldeep Ghosh, Arturo G. Pascual, Piotr Kapinos, Dana G. Mordue and Marc Y. El Khoury

Pathogens 2025, 14(4), 376; https://doi.org/10.3390/pathogens14040376 - 12 Apr 2025

Viewed by 260

Abstract

Babesiosis is an emerging tick-borne illness, and pulmonary manifestations have not been well described previously. This is a single-center, retrospective study of hospitalized adults with confirmed babesiosis at Westchester Medical Center (Valhalla, NY, USA) from 2006 to 2023. Descriptive analysis was used to [...] Read more.

Babesiosis is an emerging tick-borne illness, and pulmonary manifestations have not been well described previously. This is a single-center, retrospective study of hospitalized adults with confirmed babesiosis at Westchester Medical Center (Valhalla, NY, USA) from 2006 to 2023. Descriptive analysis was used to summarize the demographic and clinical data. Logistic regression was used to determine factors associated with severe disease and mortality. A total of 147 cases were reviewed; 63 were severe, 41 were admitted to the intensive care unit, and ten died. Respiratory symptoms were observed in 42% of cases (cough, dyspnea, oxygen supplementation, respiratory failure). A total of 55 patients had an abnormal chest radiograph (infiltrates, pleural effusions), and 75% of severe cases had parasitemia ≥ 10%. Factors associated with severe cases included age ≥ 70 years, severe dyspnea, radiographic abnormalities, white blood cell count > 5000 cells/dL, hemoglobin 8 g/dL or less, and increased creatinine. Lyme seropositivity was common (28%). Exchange transfusion did not correlate with outcome. Increased mortality was more likely in patients 70 years or older or in those having any of the following: encephalopathy, acute kidney injury, severe dyspnea on admission, abnormal chest radiograph, and requiring intubation. In conclusion, pulmonary symptoms including abnormal chest radiograph are not uncommon in babesiosis and are associated with worse outcomes. Full article

► Show Figures

Figure 1

15 pages, 1588 KiB

Open AccessArticle

The Epidemiology of Respiratory Syncytial Virus and the Impact of the COVID-19 Pandemic in a Retrospective Evaluation

by Paolo Solidoro, Antonio Curtoni, Cristina Costa, Francesco Giuseppe De Rosa, Alessandro Bondi, Francesca Sidoti, Nour Shbaklo, Filippo Patrucco, Davide Favre, Elisa Zanotto, Silvia Corcione and Rocco Francesco Rinaldo

Pathogens 2025, 14(4), 375; https://doi.org/10.3390/pathogens14040375 - 11 Apr 2025

Viewed by 239

Abstract

Introduction: Respiratory syncytial virus (RSV) is the main etiological agent in pediatric lower respiratory tract infections. The limited availability of therapeutic options for severe clinical cases associated with RSV infection makes prophylactic interventions a priority for containment. The aim of the current study [...] Read more.

Introduction: Respiratory syncytial virus (RSV) is the main etiological agent in pediatric lower respiratory tract infections. The limited availability of therapeutic options for severe clinical cases associated with RSV infection makes prophylactic interventions a priority for containment. The aim of the current study was to evaluate the epidemiology of RSV in the Piedmont population and the consequences of containment measures applied during the pandemic on viral circulation in the immediate and medium-term post-pandemic phase. Methods: This study considered all biological samples analyzed for RSV at the City of Health and Science of Turin collected from 1 January 2016 to 31 December 2023. Evaluation of the positivity rates of samples was performed and differences between pediatric and adult population swabs (nasopharyngeal, pharyngeal, nasal aspirates) and bronchoalveolar samples were reported. Results: This study analyzed 14,085 samples and highlighted a trend in Piedmont RSV infections characterized by a higher pediatric population involvement of 82% compared to the adult population at 17%. A higher number of URT infections (95%) compared to LRT infections (4.6%) was also identified. This study shows a peak in RSV cases from November to April between 2016 and 2020. Our data show no RSV positivity during the 2020/2021 winter season, a result most likely due to the influence of containment measures implemented during the COVID-19 pandemic. Conclusions: Our study provided an epidemiological panorama of RSV and its high prevalence in pediatrics and adults. Pediatrics had a higher prevalence, while adults presented a delayed trend of about one month compared to pediatrics. The effectiveness of infection control measures applied during the SARS-CoV-2 pandemic to limit viral infections were proved. Future studies may further investigate the impact of the SARS pandemic on RSV epidemiology considering patients at a higher risk of severe symptoms. Full article

(This article belongs to the Special Issue Acute Respiratory Infections: Diagnosis, Treatment, Complications and Prevention)

► Show Figures

Figure 1

12 pages, 988 KiB

Open AccessArticle

Clinical Features and Laboratory Findings of Hospitalized Children with Infectious Mononucleosis Caused by Epstein–Barr Virus from Croatia

by Laura Prtorić, Ante Šokota, Silvana Karabatić Knezović, Goran Tešović and Snjezana Zidovec-Lepej

Pathogens 2025, 14(4), 374; https://doi.org/10.3390/pathogens14040374 - 10 Apr 2025

Viewed by 226

Abstract

The aim of this retrospective 6-year study was to analyze demographic, laboratory and clinical features of 212 patients (<18 years of age) with EBV-associated infectious mononucleosis (IM) hospitalized in a tertiary clinical care center in southeastern Europe and to identify possible predictors of [...] Read more.

The aim of this retrospective 6-year study was to analyze demographic, laboratory and clinical features of 212 patients (<18 years of age) with EBV-associated infectious mononucleosis (IM) hospitalized in a tertiary clinical care center in southeastern Europe and to identify possible predictors of complications. The median patient age was 14.7 years (IQR 7.7–16.5 years), with 59.4% of patients aged between 13 and 18 years. A total of 51.2% of patients were hospitalized within 7 days following the onset of symptoms (median duration of hospitalization was 9 days, IQR 7–11 days). The most common symptoms included fever (97.16%), tonsillitis (87.3%), lymphadenopathy (79.2%), hepatomegaly (77.4%) and splenomegaly (73.1%). Symptom distribution, maximal fever and fever duration did not differ among different age groups. The most common complications included tonsillar hypertrophy, thrombocytopenia, anemia, neutropenia and leukopenia but all patients showed favorable outcomes. Patients who developed three or more complications and those presenting with thrombocytopenia showed significantly longer hospitalization durations. Platelet count, bilirubin, ESR and AST were identified as the most accurate predictors of hospitalization duration using multiple linear regression analysis. Therefore, our results suggest that clinical assessment of individual patients remains the most reliable parameter for patient management and that laboratory findings play only a supporting role. Full article

(This article belongs to the Special Issue Emerging and Neglected Pathogens in the Balkans)

► Show Figures

Figure 1

11 pages, 653 KiB

Open AccessArticle

Seroprevalence of Brucellosis in Haryana, India: A Study Using Rose Bengal Plate Test and Enzyme-Linked Immunosorbent Assay

by Dinesh Mittal, Kushal Grakh, Manesh Kumar, Punit Jhandai, Swati Dahiya, Renu Gupta, Ramesh Kumar, Anand Prakash, Pankaj Kumar, Pallavi Moudgil, Rajesh Khurana and Naresh Jindal

Pathogens 2025, 14(4), 373; https://doi.org/10.3390/pathogens14040373 - 10 Apr 2025

Viewed by 312

Abstract

Brucellosis, a contagious reproductive disease of livestock, has a significant economic impact in terms of abortions and stillbirths and has zoonotic importance. A study was conducted to estimate the seroprevalence of brucellosis in a bovine population in Haryana state, India. This study was [...] Read more.

Brucellosis, a contagious reproductive disease of livestock, has a significant economic impact in terms of abortions and stillbirths and has zoonotic importance. A study was conducted to estimate the seroprevalence of brucellosis in a bovine population in Haryana state, India. This study was carried out on 4325 bovine serum samples (Cattle: 2151, Buffalo: 2174) using the Rose Bengal Plate Test (RBPT) and indirect enzyme-linked immunosorbent assay (i-ELISA). The seroprevalence, estimated individually by the RBPT and i-ELISA, was found to be 6.86% (95% CI: 6.11–7.62) and 6.05% (95% CI: 5.34–6.76), respectively. In total, 258 out of 4325 (5.96%; 95% CI: 5.25–6.67) samples were found to be positive by both assays. The prevalence was found to be significantly higher in the cattle population (7.58%) as compared to buffalo (4.37%) (Chi-square = 19, p < 0.001). Seroprevalence was highest in the agroclimatic zone I (8.73%), followed by zone II (7.33%) and zone III (1.45%) (Chi-square = 76.27, p < 0.001). Full article

(This article belongs to the Special Issue Infection and Immunity in Animals)

► Show Figures

Figure 1

18 pages, 8680 KiB

Open AccessArticle

Recombinant Microneme Proteins MIC1 and MIC4 from Toxoplasma gondii Cause Cytotoxic Effects in the Human Jurkat T-Lymphocyte Cell Line

by Igor E. L. Souza, Maria-Cristina Roque-Barreira and Ademilson Panunto-Castelo

Pathogens 2025, 14(4), 372; https://doi.org/10.3390/pathogens14040372 - 9 Apr 2025

Viewed by 283

Abstract

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, a potentially devastating disease to fetuses and immunocompromised individuals. Among its microneme proteins, MIC1 and MIC4 play crucial roles in host-parasite interactions, facilitating adhesion by binding glycans on host cells. Beyond these roles, [...] Read more.

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, a potentially devastating disease to fetuses and immunocompromised individuals. Among its microneme proteins, MIC1 and MIC4 play crucial roles in host-parasite interactions, facilitating adhesion by binding glycans on host cells. Beyond these roles, these lectins have been implicated in modulating immune responses and inducing apoptosis, but their effects on human immune cells remain unclear. Here, we investigated the interaction of recombinant MIC1 (rMIC1) and rMIC4 with Jurkat T lymphocytes, a human immune cell model. Both lectins bound Jurkat cells in a carbohydrate-dependent manner, with rMIC4 showing competitive binding over rMIC1. Importantly, we observed that rMIC1 and rMIC4 reduced Jurkat cell viability in a time- and dose-dependent manner, inducing apoptosis through caspase activation by extrinsic and intrinsic pathways. The apoptosis was driven by reactive oxygen species production via the NADPH oxidase complex and the activation of p38 and JNK MAPK signaling pathways, emphasizing the ability of these lectins to modulate cellular signaling cascades. This study offers insights into the mechanisms involved in MIC1 and MIC4 interactions with immune cells. Full article

(This article belongs to the Section Parasitic Pathogens)

► Show Figures

Figure 1

13 pages, 442 KiB

Open AccessReview

Change of Heart: Can Artificial Intelligence Transform Infective Endocarditis Management?

by Jack W. McHugh, Douglas W. Challener and Hussam Tabaja

Pathogens 2025, 14(4), 371; https://doi.org/10.3390/pathogens14040371 - 9 Apr 2025

Viewed by 305

Abstract

Artificial intelligence (AI) has emerged as a promising adjunct in the diagnosis and management of infective endocarditis (IE), a disease characterized by diagnostic complexity and significant morbidity. Machine learning (ML) models such as SABIER and SYSUPMIE have demonstrated strong predictive accuracy for early [...] Read more.

Artificial intelligence (AI) has emerged as a promising adjunct in the diagnosis and management of infective endocarditis (IE), a disease characterized by diagnostic complexity and significant morbidity. Machine learning (ML) models such as SABIER and SYSUPMIE have demonstrated strong predictive accuracy for early IE diagnosis, embolic risk stratification, and postoperative mortality, surpassing traditional clinical scoring systems. In imaging, AI-enhanced echocardiography and advanced modalities like FDG-PET/CT offer improved sensitivity, specificity, and reduced inter-observer variability, potentially transforming clinical decision making. Additionally, AI-powered microbiological techniques, including MALDI-TOF mass spectrometry combined with ML and neural network-based metagenomic classifiers, show promise in rapidly identifying pathogens and predicting antimicrobial resistance. Despite encouraging early results, widespread adoption faces barriers, including data limitations, interpretability issues, ethical concerns, and the need for robust validation. Future directions include leveraging generative AI as clinical consultative tools, provided their capabilities and limitations are carefully managed. Ultimately, collaborative efforts addressing these challenges could transform IE care, enhancing diagnostic accuracy, clinical outcomes, and patient safety. Full article

(This article belongs to the Special Issue Updates in Infective Endocarditis—2nd Edition)

► Show Figures

Figure 1

16 pages, 2378 KiB

Open AccessCommunication

In Silico Targeting and Immunological Profiling of PpiA in Mycobacterium tuberculosis: A Computational Approach

by Mohammad J. Nasiri, Lily Rogowski and Vishwanath Venketaraman

Pathogens 2025, 14(4), 370; https://doi.org/10.3390/pathogens14040370 - 9 Apr 2025

Viewed by 350

Abstract

Tuberculosis (TB) remains a leading cause of mortality, with drug resistance highlighting the need for new vaccine targets. Peptidyl-prolyl isomerase A (PpiA), a conserved Mycobacterium tuberculosis (Mtb) protein, plays a role in bacterial stress adaptation and immune evasion, making it a potential target [...] Read more.

Tuberculosis (TB) remains a leading cause of mortality, with drug resistance highlighting the need for new vaccine targets. Peptidyl-prolyl isomerase A (PpiA), a conserved Mycobacterium tuberculosis (Mtb) protein, plays a role in bacterial stress adaptation and immune evasion, making it a potential target for immunotherapy. This study uses computational methods to assess PpiA’s antigenicity, structural integrity, and immunogenic potential. The PpiA sequence was retrieved from NCBI and analyzed for antigenicity and allergenicity using VaxiJen, AllerTOP, and AllergenFP. Physicochemical properties were evaluated using ProtParam, and structural models were generated through PSIPRED and SWISS-MODEL. Structural validation was performed with MolProbity, QMEANDisCo, and ProSA-Web. B-cell epitopes were predicted using BepiPred 2.0 and IEDB, while T-cell epitopes were mapped via IEDB’s MHC-I and MHC-II tools. Epitope conservation across Mtb strains was confirmed using ConSurf. Results indicate PpiA is highly antigenic, non-allergenic, and stable, with several immunogenic epitopes identified for both B- and T-cells. This study supports PpiA as a promising immunogenic target for TB vaccine development. Full article

(This article belongs to the Special Issue Computational Approaches in Mechanisms of Pathogenesis)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Pathogens, Volume 14, Issue 4 (April 2025) – 100 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI