Pathogens

10 pages, 2019 KiB

Open AccessBrief Report

Molecular Differentiation and Detection of AMR Genes from Nosocomial Staphylococcus spp.

by Isabelle Carneiro, Wellington Luiz Pontes da Silva, Debora Ribeiro de Souza Santos and Ivano de Filippis

Pathogens 2025, 14(5), 403; https://doi.org/10.3390/pathogens14050403 - 23 Apr 2025

Abstract

Staphylococcus spp. is a major nosocomial pathogen, particularly affecting immunocompromised patients and infants. It is associated with bacteremia, endocarditis, and co-infections. Methicillin-resistant Staphylococci (MRS) carry the mecA gene, encoding PBP2a, which confers resistance to beta-lactam antibiotics. The aim of this study is to [...] Read more.

Staphylococcus spp. is a major nosocomial pathogen, particularly affecting immunocompromised patients and infants. It is associated with bacteremia, endocarditis, and co-infections. Methicillin-resistant Staphylococci (MRS) carry the mecA gene, encoding PBP2a, which confers resistance to beta-lactam antibiotics. The aim of this study is to investigate resistance profiles and develop a molecular method to identify nosocomial Staphylococcus spp. strains. A total of 64 strains from public hospitals in Rio de Janeiro were analyzed using phenotypic and molecular methods, with 17 classified as MDR. Different melting temperatures (Tm) were obtained through qPCR-HRM analysis, to identify S. aureus- (70.4 °C), S. haemolyticus- (79 °C), S. epidermidis- (74.1 °C) and mecA (70.5 °C)-positive strains (MRS). The mecA gene was detected in 51 strains, with 22 showing SCCmec type IV. The spread of MRSA and MDR Staphylococci, particularly MDR S. haemolyticus, is a growing concern. In our study, among 64 Staphylococci strains, only 11 were susceptible to methicillin, showing the continuous emergence of resistant strains. qPCR-HRM is a cost-effective, sensitive and fast method for rapid Staphylococcus spp. identification, aiding in nosocomial infection control. Full article

(This article belongs to the Special Issue Nosocomial Infections and Antimicrobial Resistance: Challenges and Solutions)

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19 pages, 3425 KiB

Open AccessArticle

Microbiological Risks to Health Associated with the Release of Antibiotic-Resistant Bacteria and β-Lactam Antibiotics Through Hospital Wastewater

by Andres E. Nolasco-Rojas, Eder Cruz-Del-Agua, Clemente Cruz-Cruz, Miguel Ángel Loyola-Cruz, Benjamín A. Ayil-Gutiérrez, María C. Tamayo-Ordóñez, Yahaira de J. Tamayo-Ordoñez, Araceli Rojas-Bernabé, Francisco A. Tamayo-Ordoñez, Emilio M. Durán-Manuel, Marianela Paredes-Mendoza, Laura M. Márquez-Valdelamar, Carlos A. Jiménez-Zamarripa, Esther Ocharan-Hernández, Paola B. Zárate-Segura, Omar García-Hernández, Oscar Sosa-Hernández, Enzo Vásquez-Jiménez, Claudia C. Calzada-Mendoza and Juan M. Bello-López

Pathogens 2025, 14(5), 402; https://doi.org/10.3390/pathogens14050402 - 23 Apr 2025

Abstract

Hospital wastewater (HWW) is a major source of microbiological contamination, often released into the municipal sewage system without prior treatment. This HWW may contain pathogens with antimicrobial resistance, posing risks to public health. The aim of this work was to assess the risks [...] Read more.

Hospital wastewater (HWW) is a major source of microbiological contamination, often released into the municipal sewage system without prior treatment. This HWW may contain pathogens with antimicrobial resistance, posing risks to public health. The aim of this work was to assess the risks associated with the seasonal release of ESKAPE bacteria resistant to β-lactam antibiotics and the release of carbapenems and cephalosporins through HWW of Hospital Juárez de México. The 12-month seasonal variation in β-lactam-resistant bacterial populations was assessed in the HWW of five discharge points. Resistant isolates were identified by mass spectrometry (MALDI-TOF) coupled with PCR assays to search for antimicrobial resistance genes, while β-lactamic antibiotics were detected using high-performance liquid chromatography (HPLC). Finally, a double-entry Vester matrix was constructed to classify the problems of HWW according to their degree of causality. Seasonal differences in bacterial loads were observed, with higher levels in warmer months. A wide variety of resistant pathogens were identified, including ESKAPE bacteria, as well as emerging bacteria carrying β-lactamase-encoding genes. The release of meropenem was detected most commonly, followed by cefepime and ceftazidime. The Vester matrix allowed the identification of critical clinical and environmental scenarios where two discharge points contribute significantly to the spread of microbiological contamination. This study highlights the importance of proper management of HWW and the need for stricter regulations to reduce the risks associated with the release of resistant pathogens with health impacts. Full article

(This article belongs to the Special Issue Nosocomial Infections and Antimicrobial Resistance: Challenges and Solutions)

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16 pages, 1077 KiB

Open AccessArticle

Antimicrobial Evaluation of Asphodelus microcephalus Extracts and Fine Powder of Dried Organs Against Fusarium and Oomycetes Responsible for Apple and Peach Decline Disease

by Sabrine Mannai and Naima Boughalleb-M’Hamdi

Pathogens 2025, 14(5), 401; https://doi.org/10.3390/pathogens14050401 - 22 Apr 2025

Abstract

Seedlings root and collar rot is an important disease that causes a reduction in plant production. The goal of this investigation was to evaluate the in vitro and in vivo efficiency of powdered preparation of dried Asphodelus microcephalus of fruits (PPDF), leaves (PPDL), [...] Read more.

Seedlings root and collar rot is an important disease that causes a reduction in plant production. The goal of this investigation was to evaluate the in vitro and in vivo efficiency of powdered preparation of dried Asphodelus microcephalus of fruits (PPDF), leaves (PPDL), and roots (PPDR) against species of Fusarium and Pythiaceaes associated with this disease in Tunisian nurseries. The in vitro tests of methanolic and aqueous extracts of different Asphodelus organs showed their efficacy in reducing the pathogen mycelium growth. The in vivo assay of powdered preparation of this dried plant revealed that its effect depends on the pathogens, Asphodelus organs, and the period duration between the treatment and inoculation of seedlings. This study showed that this plant has some positive effects, such as disease severity reduction and plant growth stimulation. In fact, for Fusarium solani, the powder of different organs of Asphodelus was used one week before the plantation, and inoculation significantly improved the peach plant’s height. The treatments eight weeks before the inoculation enhanced the root weight of the plants. Meanwhile, the PPDL and PPDR were used eight weeks before the plantation, and inoculation induced the plant disease index. However, the A. microcephalus treatments also have some toxic effects on peach and apple seedlings, such as the improvement of root browning induced by some pathogens. Full article

(This article belongs to the Section Fungal Pathogens)

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8 pages, 2999 KiB

Open AccessCommunication

Diagnosis of Community-Acquired Pneumonia Due to Influenza or Respiratory Syncytial Virus: Evaluation of RT-PCR Sensitivity in Nasopharyngeal, Saliva, and Sputum Samples

by Julio Ramirez, Stephen Furmanek, Thomas Chandler, Ruth Carrico, Ashley Wilde, Alan Junkins and Anupama Raghuram

Pathogens 2025, 14(5), 400; https://doi.org/10.3390/pathogens14050400 - 22 Apr 2025

Abstract

Detection of viral RNA in nasopharyngeal (NP) samples by reverse transcription polymerase chain reaction (RT-PCR) is the standard diagnostic test for influenza or respiratory syncytial virus (RSV) in hospitalized patients with community-acquired pneumonia (CAP). This study compared the sensitivity of RT-PCR using NP [...] Read more.

Detection of viral RNA in nasopharyngeal (NP) samples by reverse transcription polymerase chain reaction (RT-PCR) is the standard diagnostic test for influenza or respiratory syncytial virus (RSV) in hospitalized patients with community-acquired pneumonia (CAP). This study compared the sensitivity of RT-PCR using NP swab, saliva, and sputum samples for the diagnosis of CAP due to influenza or RSV. A total of 60 patients were evaluated, of which 40 (67%) had influenza CAP, 19 (32%) had RSV CAP, and one patient (1%) had both RSV and influenza CAP. RT-PCR on NP swab, saliva, and sputum samples was performed using the Luminex ARIES platform. In patients with influenza CAP, the sensitivity was 34% for NP swabs, 68% for saliva, and 71% for sputum. In patients with RSV CAP, the sensitivity was 60% for NP swabs, 75% for saliva, and 85% for sputum. RT-PCR of nasopharyngeal swab samples was associated with a significant number of false negative results. A negative NP swab RT-PCR test should not be used to rule out CAP due to influenza or RSV. Saliva and sputum samples should be considered when performing a microbiological work-up in patients with suspected influenza or RSV CAP. Full article

(This article belongs to the Section Viral Pathogens)

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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

Abstract

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)

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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)

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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

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)

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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

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

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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

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

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)

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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

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)

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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

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)

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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

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)

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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

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)

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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

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)

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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

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)

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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

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)

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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

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

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