Pathogens

24 pages, 1143 KB

Open AccessReview

Tackling Biofilm-Forming Pathogens: A Challenge to Overcome in the Fight Against Infectious Diseases

by Elenoire Sole, Giuseppe Motta, Federica Marcoli, Angelina Midiri, Cinzia Sindona, Liliana Imbesi, Giuseppe Mancuso, Mohamed Zemzem and Carmelo Biondo

Pathogens 2026, 15(5), 493; https://doi.org/10.3390/pathogens15050493 (registering DOI) - 3 May 2026

Abstract

Microorganisms can aggregate and organise into structured communities embedded within an exopolysaccharide-based matrsix, which serves as a protective barrier and a functional environment around microbial cells. The formation of biofilms is widely recognised as a pivotal factor in bacterial virulence, impeding the efficacy [...] Read more.

Microorganisms can aggregate and organise into structured communities embedded within an exopolysaccharide-based matrsix, which serves as a protective barrier and a functional environment around microbial cells. The formation of biofilms is widely recognised as a pivotal factor in bacterial virulence, impeding the efficacy of antimicrobial agents and hindering immune responses, whilst concomitantly contributing to the development of antimicrobial resistance and the onset of persistent infections. Biofilm formation is a tightly regulated and dynamic process, controlled by quorum-sensing mechanisms and profoundly influenced by environmental factors and nutrient availability. The objective of this review is to elucidate the significance of biofilms in clinical settings, with a particular focus on their role in the pathogenesis of infectious diseases. Particular attention is devoted to biofilm-associated infections and infections related to invasive medical devices, with a particular emphasis on the most prevalent microbial pathogens, which include S. aureus, S. epidermidis, P. aeruginosa, E. coli, K. pneumoniae, A. baumannii and various species of Candida. Furthermore, the present review encompasses biofilm-associated chronic infections, conditions manifesting in predisposed patients, including individuals affected by cystic fibrosis. This review further examines the most recent strategies for combating antibiotic resistance in bacterial biofilms. This review focuses on recent biofilm pathogenesis advancements, with a focus on diagnosis challenges and the need for new ways to disrupt biofilm integrity. Full article

(This article belongs to the Special Issue Epidemiology of Bacterial Pathogens)

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15 pages, 477 KB

Open AccessArticle

Clinical Characteristics and Outcomes of Cytomegalovirus DNAemia in Non-HIV-Infected and Non-Transplant Patients: A Propensity Score-Matched Analysis

by Ixchel Salter, Michaele-Francesco Corbisiero, Daniel B. Chastain, Chia-Yu Chiu, Leland Shapiro, Jose G. Montoya, Raymund R. Razonable and Andrés F. Henao-Martínez

Pathogens 2026, 15(5), 492; https://doi.org/10.3390/pathogens15050492 - 1 May 2026

Abstract

Cytomegalovirus (CMV) establishes lifelong latency following primary infection and can reactivate to cause severe illness in immunocompromised hosts. CMV DNAemia in non-HIV-infected, non-solid organ/bone marrow transplant (NHNT) hosts is poorly characterized, with limited clinical insights. We aim to describe the clinical presentation, prognostic [...] Read more.

Cytomegalovirus (CMV) establishes lifelong latency following primary infection and can reactivate to cause severe illness in immunocompromised hosts. CMV DNAemia in non-HIV-infected, non-solid organ/bone marrow transplant (NHNT) hosts is poorly characterized, with limited clinical insights. We aim to describe the clinical presentation, prognostic indicators, and outcomes of CMV DNAemia among NHNT patients. We used the TriNetX international patient database to identify adult patients diagnosed with CMV DNAemia from 2016 until March 2023. We evaluated hospitalization, intensive care unit (ICU) level care, and all-cause mortality at 30 days and 1 year. We also completed a post-propensity score analysis comparing clinical characteristics of survivors versus non-survivors at 90 days. We identified 1123 NHNT patients with CMV DNAemia, most of whom had neoplasms (63%). Venous thromboembolism occurred in 31% of the population. The 30-day hospitalization and all-cause mortality rates were 35% and 14%, respectively. After propensity score matching and Bonferroni correction, weakness, purpura, acute respiratory failure, malnutrition, encephalopathy, and hypotension were associated with increased 90-day all-cause mortality. NHNT patients with CMV DNAemia carry a substantial morbidity and all-cause mortality. Further studies are warranted to clarify whether CMV DNAemia is a causative factor or an incidental finding in this population. Full article

(This article belongs to the Special Issue Viral Infections in Immunocompromised Patients)

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16 pages, 1284 KB

Open AccessArticle

Phellodendron amurense Leaf Extract Inhibits Rhabdovirus Infection by Targeting Early Stages of Viral Entry

by Su Yeon Kim, Taek-Kyun Lee and Tae-Jin Choi

Pathogens 2026, 15(5), 491; https://doi.org/10.3390/pathogens15050491 - 1 May 2026

Abstract

RNA viruses exhibit high mutation rates, necessitating antivirals targeting conserved infection mechanisms. In this study, viral hemorrhagic septicemia virus (VHSV), a non-human pathogenic negative-sense RNA virus, was used as a surrogate model to enable high-throughput antiviral screening under reduced biosafety conditions. A recombinant [...] Read more.

RNA viruses exhibit high mutation rates, necessitating antivirals targeting conserved infection mechanisms. In this study, viral hemorrhagic septicemia virus (VHSV), a non-human pathogenic negative-sense RNA virus, was used as a surrogate model to enable high-throughput antiviral screening under reduced biosafety conditions. A recombinant VHSV expressing enhanced green fluorescent protein was used to screen 17,265 compounds, 2000 plant extracts, and 100 marine extracts. Among the candidates, the leaf extract of Phellodendron amurense Rupr. (PL extract) exhibited antiviral activity with low cytotoxicity (selectivity index ≈ 10). The extract reduced viral infectivity in a dose-dependent manner and showed cross-activity against snakehead rhabdovirus. Mechanistic analyses indicated that the PL extract acts primarily at early stages of infection. Virucidal assays demonstrated direct, time-dependent inactivation of viral particles, while pre-treatment reduced host cell susceptibility. Time-of-addition experiments confirmed that antiviral activity was restricted to early infection, suggesting interference with viral attachment or entry rather than intracellular replication. Fractionation revealed that activity was associated with the non-polar n-hexane fraction, implicating lipophilic compounds that may disrupt viral envelope integrity or membrane interactions. These findings suggest that P. amurense leaf extract is a promising candidate for broad-spectrum antivirals targeting conserved entry processes in enveloped RNA viruses. Full article

(This article belongs to the Special Issue Advances in Virology of Aquatic Animal Viruses)

19 pages, 2382 KB

Open AccessReview

Functional Antibody-Dependent Enhancement as an Immune Assessment Platform: Development, Standardization, and Translational Interpretation in Flavivirus Research

by Meng Ling Moi

Pathogens 2026, 15(5), 490; https://doi.org/10.3390/pathogens15050490 - 1 May 2026

Abstract

Functional antibody-dependent enhancement (ADE) represents a fundamental and context-dependent characteristic of antiviral antibody responses, reflecting the dual capacity of antibodies to mediate both the neutralization and Fc receptor-dependent enhancement of infection. In flavivirus research, this duality complicates the interpretation of conventional serological metrics [...] Read more.

Functional antibody-dependent enhancement (ADE) represents a fundamental and context-dependent characteristic of antiviral antibody responses, reflecting the dual capacity of antibodies to mediate both the neutralization and Fc receptor-dependent enhancement of infection. In flavivirus research, this duality complicates the interpretation of conventional serological metrics and limits the reliability of single-parameter correlates of immunity, particularly in populations with complex exposure histories. Over the past decade, functional ADE assays have evolved from specialized mechanistic tools into integrated immune assessment platforms supporting translational immunology, vaccine evaluation, and population-level immune surveillance. These platforms incorporate Fcγ receptor-relevant target cell systems, standardized viral inputs, dilution series-based profiling, quantitative enhancement metrics, and structured quality control frameworks to enable reproducible, comparable, and context-aware functional measurements across cohorts and laboratories. A central concept emerging from these developments is that ADE reflects a dynamic functional immune state rather than an intrinsic property of antibodies or a direct indicator of pathological risk. Accordingly, functional ADE platforms support the contextual interpretation of antibody activity across physiologically relevant conditions, facilitating discrimination between transient functional enhancement and clinically meaningful immunological risk. By integrating functional ADE metrics with serological, cellular, and epidemiological data, these platforms provide a structured framework for interpreting immune profiles in vaccine evaluation, booster strategy design, and population-level risk stratification. This review synthesizes the development, standardization, and global dissemination of functional ADE platforms and discusses key principles governing biological relevance, analytical robustness, and inter-site transferability. Emerging directions integrating functional ADE profiling with systems immunology, immunogenomics, and computational modeling are highlighted as pathways toward predictive, decision-support-oriented frameworks. By positioning ADE platforms as immune assessment infrastructures rather than isolated assays, this review underscores their value for mechanistic inquiry, translational interpretation, and preparedness-oriented responses to emerging viral threats in the absence of definitive correlates of protection. Full article

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26 pages, 1601 KB

Open AccessReview

RISK6 as a Translational Host Transcriptomic Signature for Tuberculosis Diagnosis, Treatment Monitoring, and Risk Stratification

by Chrispian Mamudi, Purnamawati, Panca Andana, Prayudi Santoso, Lidya Chaidir and Arto Soeroto

Pathogens 2026, 15(5), 489; https://doi.org/10.3390/pathogens15050489 - 1 May 2026

Abstract

Tuberculosis (TB) remains a leading cause of infectious mortality worldwide, reflecting persistent gaps in diagnosis, risk stratification, and treatment monitoring. Host RNA transcriptomic signatures have emerged as promising tools for capturing dynamic immune responses across the TB disease spectrum. Among these, the six-gene [...] Read more.

Tuberculosis (TB) remains a leading cause of infectious mortality worldwide, reflecting persistent gaps in diagnosis, risk stratification, and treatment monitoring. Host RNA transcriptomic signatures have emerged as promising tools for capturing dynamic immune responses across the TB disease spectrum. Among these, the six-gene RISK6 signature has attracted attention due to its parsimonious design and potential for clinical translation. This review provides a clinically oriented synthesis of current evidence on host transcriptomic biomarkers, with a particular focus on the application of RISK6 in diagnosis, prediction of disease progression, and treatment monitoring. Available data suggest that RISK6 demonstrates promising but context-dependent diagnostic performance and represents a versatile host-response biomarker across multiple clinical applications. However, variability across populations and the limited evidence in multidrug-resistant TB remain important constraints. In practice, RISK6 is unlikely to function optimally as a standalone biomarker. Its clinical value appears greater when interpreted within integrated frameworks that combine transcriptomic, microbiological, and clinical data. Further validation in diverse populations and real-world settings will be essential to support meaningful clinical implementation. Full article

(This article belongs to the Section Bacterial Pathogens)

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17 pages, 3973 KB

Open AccessReview

Formulation Strategies for Fungal Biocontrol of Gastrointestinal Helminths in Domestic Animals and Plant-Parasitic Nematodes: A Review

by Júlia dos Santos Fonseca, Tábata Alves do Carmo, Bianca de Oliveira Botelho Vital, Thalita Suelen Avelar Monteiro, Huarlen Marcio Balbino, Huarrisson Azevedo Santos, Vagner Tebaldi de Queiroz, Fabio Ribeiro Braga and Jackson Victor de Araújo

Pathogens 2026, 15(5), 488; https://doi.org/10.3390/pathogens15050488 - 1 May 2026

Abstract

Although microbial biopesticides are expanding rapidly, transforming nematophagous fungi into consistent and shelf-stable products remains a challenge. A key limitation is that fungal propagules must remain viable throughout production, storage, and delivery to ensure their efficacy in the field. This review examines formulation [...] Read more.

Although microbial biopesticides are expanding rapidly, transforming nematophagous fungi into consistent and shelf-stable products remains a challenge. A key limitation is that fungal propagules must remain viable throughout production, storage, and delivery to ensure their efficacy in the field. This review examines formulation strategies that improve the stability, deployment, and performance of fungal biocontrol agents against gastrointestinal helminths in domestic animals and plant-parasitic nematodes. In veterinary systems, predatory fungi such as Duddingtonia flagrans primarily target infective larvae after surviving gastrointestinal transit and germination in feces. In contrast, ovicidal fungi, including Pochonia chlamydosporia, Purpureocillium lilacinum, Trichoderma spp., and Mucor spp., primarily act against helminth eggs and coccidian oocysts. This functional complementarity highlights the potential of combined fungal formulations to improve their control efficacy. We also discuss the currently available D. flagrans-based commercial products, BioWorma^® and Bioverm^®, and the practical challenges associated with dosing, administration, and farm adoption. In agriculture, we show that the Brazilian market is dominated by solid fungal nematicides designed to reduce water activity and prolong shelf life, although liquid- and oil-based systems remain relevant for specific applications. Across both sectors, the review identified formulation design, rather than fungal species alone, as a critical determinant of product performance. Emerging advances, such as microencapsulation, UV-protective matrices, improved seed-coating biopolymers, nanobiotechnology, and fungal-derived bioactive products, indicate that future progress will depend on target-oriented formulations capable of increasing stability, controlled release, and resilience under environmentally variable conditions, including those imposed by climate change. Full article

(This article belongs to the Special Issue Parasitic Helminths and Control Strategies)

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13 pages, 733 KB

Open AccessArticle

Increased Expression of CXCL9, CXCL10, and CXCL11 in Epstein–Barr Virus-Associated Infectious Mononucleosis and the Role of CXCL5 as a Candidate Biomarker of Disease Severity

by Andrea Nikčević, Leona Radmanić Matotek, Silva Šiftar, Lorna Stemberger Marić, Goran Tešović and Snjezana Zidovec-Lepej

Pathogens 2026, 15(5), 487; https://doi.org/10.3390/pathogens15050487 - 1 May 2026

Abstract

Background: Epstein–Barr virus (EBV)-associated infectious mononucleosis (IM) elicits a robust cellular immune response; however, systemic chemokine profiles in pediatric IM and their diagnostic relevance remain insufficiently characterized. This study evaluated proinflammatory chemokine expression in children with acute EBV-associated IM and its relationship with [...] Read more.

Background: Epstein–Barr virus (EBV)-associated infectious mononucleosis (IM) elicits a robust cellular immune response; however, systemic chemokine profiles in pediatric IM and their diagnostic relevance remain insufficiently characterized. This study evaluated proinflammatory chemokine expression in children with acute EBV-associated IM and its relationship with disease presence and severity. Methods: In this retrospective study, 64 children with confirmed acute EBV-associated IM and 16 healthy controls were included. Clinical severity was classified using the Severity of Mononucleosis (SOM) scale. Plasma concentrations of 12 chemokines were quantified by bead-based flow cytometry. Groups were compared using nonparametric tests, and logistic regression with cross-validation identified predictors distinguishing IM from controls. Results: CXCL9, CXCL10, and CXCL11 concentrations were significantly elevated in IM patients compared with controls across all severity strata (p ≤ 0.011), with no differences between SOM categories. CXCL5 concentrations were lower in severe (SOM ≥ 2) than moderate disease (p = 0.037). Other chemokines showed no significant differences. CXCL9 and CXCL10 effectively distinguished IM (AUC = 0.86, sensitivity = 0.71, specificity = 0.96). Conclusions: IFN-γ–inducible chemokines CXCL9–11 are markedly elevated in pediatric EBV-associated IM, irrespective of clinical severity, whereas CXCL5 may be associated with disease severity. Prospective validation of these preliminary findings is strongly warranted. Full article

(This article belongs to the Section Viral Pathogens)

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12 pages, 2445 KB

Open AccessArticle

Differential Interactions of Tissue-Restricted Host Proteins SPLUNC1 and VAMP8 with VP3 of Human Bocaviruses 1 and 2

by Ri De, Yanpeng Xu, Hanhaoyu Fu, Liping Jia and Linqing Zhao

Pathogens 2026, 15(5), 486; https://doi.org/10.3390/pathogens15050486 - 1 May 2026

Abstract

Background: Four genotypes of human bocaviruses (HBoVs) have been identified, with only HBoV1 being detected in respiratory specimens, and with HBoV2 being the predominant human bocavirus in fecal specimens, which implies different tissue tropisms for HBoV1 and HBoV2. It is vital to determine [...] Read more.

Background: Four genotypes of human bocaviruses (HBoVs) have been identified, with only HBoV1 being detected in respiratory specimens, and with HBoV2 being the predominant human bocavirus in fecal specimens, which implies different tissue tropisms for HBoV1 and HBoV2. It is vital to determine the factors that influence the tissue tropisms. Methods: The major capsid proteins VP3 of HBoV1 and HBoV2 were expressed in eukaryotic cells. Then co-immunoprecipitation (Co-IP) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) (IP-MS) was employed, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, to screen host proteins interacting with VP3 of different genotypes. Subsequently, in vitro pull-down assays were conducted to verify the direct virus–host interaction proteins with VP3. Furthermore, molecular docking was performed to predict the interaction interfaces between viral and host proteins. Results: Through IP-MS and enrichment analyses, 50 host proteins that displayed ≥10-fold differential binding affinities between HBoV1 VP3 and HBoV2 VP3 were identified. Among these, seven were considered as high-confidence candidate interactors. Notably, SPLUNC1 and VAMP8 showed predominant expression in respiratory and intestinal tissues, respectively. Subsequent in vitro pull-down assays confirmed that SPLUNC1 specifically bound to HBoV1 VP3, whereas VAMP8 specifically interacted with HBoV2 VP3. Molecular docking analysis further revealed that the binding between SPLUNC1 with HBoV1 VP3, as well as VAMP8 with HBoV2 VP3, was stabilized by extensive hydrophobic interfaces along with specific hydrogen bonds. Conclusions: The specific interactions of host proteins SPLUNC1 with HBoV1 VP3 and VAMP8 with HBoV2 VP3, respectively, provided fundamental evidence that the distinct tissue tropisms of HBoVs may be governed by specific host factors. Full article

(This article belongs to the Special Issue Advanced Research on Human Viral Coinfections)

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17 pages, 4797 KB

Open AccessArticle

Viral Risks at the Human–Bat Interface: Household Bat Guano Farming in Rural Cambodia

by Theara Teng, Sarin Neang, Bruno M. Ghersi, Cora Cunningham, Daniel Nguyen, Felicia B. Nutter, Veasna Duong, Thavry Hoem, Sothyra Tum, Theary Ren, Dina Koeut, Sam Eang Huon, Sothealy Oeun, Jonathon D. Gass, Janetrix Hellen Amuguni, Daniele Lantagne and Tristan L. Burgess

Pathogens 2026, 15(5), 485; https://doi.org/10.3390/pathogens15050485 - 30 Apr 2026

Abstract

In Cambodia, farmers construct artificial household bat roosts to collect and sell guano as fertilizer. We investigated farming practices and attendant spillover risks using (1) surveys on guano production; (2) an estimation of bat population size and species present using carcasses, visual identification, [...] Read more.

In Cambodia, farmers construct artificial household bat roosts to collect and sell guano as fertilizer. We investigated farming practices and attendant spillover risks using (1) surveys on guano production; (2) an estimation of bat population size and species present using carcasses, visual identification, and audio recordings; (3) surveys of guano-producing and neighboring households on water, sanitation, and hygiene practices; and (4) the testing of guano and household food, water, and surfaces for coronaviruses using RT-qPCR. Bat roosts are constructed using dried palm leaves with coconut tree and/or steel/concrete supports. Roosting areas ranged from 42 to 327 m², bat abundance varied from 0 to 11,187, guano production was between 5 and 120 kg/week, guano yields were from 0.15 to 0.4 kg/m²/week, and farmers earned USD ~100–200/household/month. Higher guano production in the peak (normally wet) season was associated with greater bat abundance (p = 0.016). The lesser Asiatic yellow house bat (Scotophilus kuhlii) was the only bat species identified. Roosts were <20 m from guano-producing households. Neighbors and households’ hygiene risks included not having handwashing stations and not covering food in storage/while drying. Coronaviruses (Alphacoronaviruses or Infectious Bronchitis Virus) were detected in 14.6%, 17.3%, 2.9%, 1.4%, and 0.0% of guano, urine, household surface, food, and water samples, respectively. While guano farming offers economic benefits, spillover risks exist. Safe guano collection and storage, handwashing, and food covering in guano-producing communities are necessary to mitigate spillover risks. Full article

(This article belongs to the Section Viral Pathogens)

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15 pages, 900 KB

Open AccessArticle

Efficacy of Certain Monoterpenes as Antifungal Agents and Abiotic Elicitors Against Chocolate Spot Disease of Faba Beans Caused by Botrytis fabae

by Aly Derbalah, Ahmed Mohamed, Nehad El-Gammal, Warda Hussain, Amany Hamza, Ahmed Alhusays, Ayman Omar and Saleh Alhewairini

Pathogens 2026, 15(5), 484; https://doi.org/10.3390/pathogens15050484 - 30 Apr 2026

Abstract

Chocolate spot, caused by the ascomycete fungus Botrytis fabae, is a devastating foliar disease and a major constraint on the quality and yield of faba beans (Vicia faba). Monoterpenes, such as carvone, cineole, and linalool, are often considered natural-identical alternatives [...] Read more.

Chocolate spot, caused by the ascomycete fungus Botrytis fabae, is a devastating foliar disease and a major constraint on the quality and yield of faba beans (Vicia faba). Monoterpenes, such as carvone, cineole, and linalool, are often considered natural-identical alternatives to synthetic chemicals. Therefore, this study was carried out to assess the antifungal activity of some eco-friendly control agents (carvone, cineole, and linalool) against B. fabae, the causative agent of chocolate spot disease in faba beans, through growth inhibition assays in vitro. Furthermore, the efficacy of the tested monoterpenes for reducing the severity of chocolate spot disease in faba beans was evaluated under field conditions. Moreover, these eco-friendly control agents activate plant defense enzymes (phenylalanine ammonia-lyase, polyphenol oxidase, and peroxidase) as a self-defense mechanism against pathogen attacks of faba bean plants were investigated. Moreover, the impact of the tested monoterpenes on growth and yield characters of faba bean was evaluated. The results indicated a significant decrease in B. fabae growth following a treatment with the tested compounds compared to untreated controls. In field trials, treated faba bean plants exhibited a notable reduction in disease severity. Additionally, the application of monoterpenes enhanced the activity of defense enzymes (phenylalanine ammonia-lyase, polyphenol oxidase, and peroxidase), which are integral to plant defense mechanisms. Treatments also resulted in significant improvement growth and yield characters of faba bean. These findings suggest that the tested monoterpenes could serve as a control strategy for managing B. fabae, offering an environmentally sustainable alternative to conventional fungicides. Full article

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27 pages, 1058 KB

Open AccessReview

Pathogenic Roles of Fusobacterium nucleatum in Colorectal Cancer: From Strain Heterogeneity to Host–Pathogen Interactions

by Ruihong Xiao, Yanrui Bai, Wenxiu Liu and Hui Sun

Pathogens 2026, 15(5), 483; https://doi.org/10.3390/pathogens15050483 - 30 Apr 2026

Abstract

Fusobacterium nucleatum (Fn) has emerged as one of the most extensively studied tumor-associated opportunistic pathogens in colorectal cancer (CRC). The central question in Fn–CRC research has shifted from species-level detection or enrichment toward identifying specific lineages with enhanced persistence and tumor-promoting potential under [...] Read more.

Fusobacterium nucleatum (Fn) has emerged as one of the most extensively studied tumor-associated opportunistic pathogens in colorectal cancer (CRC). The central question in Fn–CRC research has shifted from species-level detection or enrichment toward identifying specific lineages with enhanced persistence and tumor-promoting potential under defined host and ecological contexts. Accumulating evidence suggests substantial heterogeneity within Fn at the subspecies and clade levels. Among these, the F. nucleatum subsp. animalis C2 (Fna C2) lineage has been proposed as a candidate high-risk clade with potentially greater adaptability to the gastrointestinal tract and tumor microenvironment. However, current support for Fna C2 is derived mainly from ecological enrichment, comparative genomics, inferred metabolic features, and limited functional observations, while direct clinical and mechanistic validation at the clade level remains limited. Fn has been implicated in CRC progression through multiple interconnected processes, including adhesion and colonization, host signaling activation, inflammatory amplification, immune suppression, and metabolic adaptation. Notably, these pathogenic outputs are unlikely to be uniformly distributed across all Fn lineages, but instead appear to be shaped by the combined influence of bacterial lineage, host molecular context, microbial community structure, and spatial organization within the tumor microenvironment. In this review, we summarize the lineage heterogeneity of Fn, its association with CRC, and the underlying host–pathogen interaction mechanisms. We further discuss implications for high-resolution stratification, risk classification, and clinical translation, emphasizing the need to move from species-level associations toward lineage-resolved and context-aware frameworks. Full article

(This article belongs to the Section Bacterial Pathogens)

14 pages, 13287 KB

Open AccessArticle

Food Deprivation in Triatoma pallidipennis Increases the Expression of α-Tubulin, β-Actin, and a Heat Shock Protein in the Anterior Midgut

by Olivia Alicia Reynoso-Ducoing, Elsa Gabriela Díaz-Ramírez, Elia Torres-Gutiérrez, Mauro Omar Vences-Blanco, Berenice González-Rete, Yolanda Guevara-Gómez, Margarita Cabrera-Bravo and Paz María Silvia Salazar-Schettino

Pathogens 2026, 15(5), 482; https://doi.org/10.3390/pathogens15050482 - 30 Apr 2026

Abstract

Food deprivation induces intestinal adaptations in Triatoma pallidipennis, a hematophagous insect with intermittent feeding habits. The ability to survive long periods without food promotes the persistence of this vector in the environment and contributes to its evolutionary success. This study employed one- [...] Read more.

Food deprivation induces intestinal adaptations in Triatoma pallidipennis, a hematophagous insect with intermittent feeding habits. The ability to survive long periods without food promotes the persistence of this vector in the environment and contributes to its evolutionary success. This study employed one- and two-dimensional electrophoretic techniques combined with Western blot to evaluate the abundance of α-tubulin, β-actin, and the heat shock protein HSP70. These proteins were more abundant in the anterior midgut tissue of unfed insects than in that of fed insects. As these responses were similar in females and males, the observed adaptations primarily depend on feeding status and intestinal region. These findings provide further insight into the intestinal physiology of T. pallidipennis, a vector of the flagellate parasite Trypanosoma cruzi, the causative agent of Chagas disease. Full article

(This article belongs to the Special Issue Diagnosis, Prevention, and Treatment of Leishmaniasis and Chagas Disease: Focus on Latin American Context)

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2 pages, 134 KB

Open AccessCorrection

Correction: Wahdan et al. One Health Monitoring of Resistant Pseudomonas aeruginosa in Aquatic, Poultry, and Human Sources: Virulence Traits and bla_SHV Gene Tracking. Pathogens 2025, 14, 983

by Ali Wahdan, Mahmoud Ezzat, Amal Emam, Walaa A. Husseiny, Mohamed Abou El-Atta, Ehab M. Abd-Allah, Ahmed M. A. Meligy, Sherief M. Abdel-Raheem, Faisal Almathen, Salah Al-Shami, Saad I. Al-Sultan, Ahmed Alfifi, Wael El-Deeb and Marwa E. Abo Hashem

Pathogens 2026, 15(5), 481; https://doi.org/10.3390/pathogens15050481 - 30 Apr 2026

Abstract

This notice provides additional clarification to the original publication [...] Full article

14 pages, 1114 KB

Open AccessArticle

Outbreak Investigation of Pseudomonas aeruginosa Endophthalmitis Following Cataract Surgery in a Private Ophthalmology Clinic in Korea

by Min A Lim, Na Young Hong, Sook Hee Park, Myung Hee Kim, Youkyoung Kim, Ji Hong Park, Dong Gyu Park, Hee Young Hwang, Seok Ju Yoo, Ji Hyuk Park and Kwan Lee

Pathogens 2026, 15(5), 480; https://doi.org/10.3390/pathogens15050480 - 29 Apr 2026

Abstract

Postoperative endophthalmitis is a rare but severe complication of cataract surgery that may lead to significant visual impairment and can occasionally present as clusters or outbreaks linked to lapses in infection control. On 29 October 2025, three cases of postoperative endophthalmitis following cataract [...] Read more.

Postoperative endophthalmitis is a rare but severe complication of cataract surgery that may lead to significant visual impairment and can occasionally present as clusters or outbreaks linked to lapses in infection control. On 29 October 2025, three cases of postoperative endophthalmitis following cataract surgery at an ophthalmology clinic (Clinic A) in Yeongju, Republic of Korea, were reported to public health authorities. All cases were confirmed as Pseudomonas aeruginosa (P. aeruginosa). An epidemiological investigation was conducted to identify the source and transmission route; all 54 patients who underwent cataract surgery at Clinic A in October 2025 (62 procedures, including eight bilateral cases) were included. Infection control practices were assessed through on-site inspection, staff interviews, medical record review, and telephone surveys. Environmental samples were collected and cultured selectively for P. aeruginosa. Isolates were analyzed using pulsed-field gel electrophoresis (PFGE) to assess genetic relatedness. Among 54 surgical patients, three developed endophthalmitis (attack rate: 5.6%). All cases occurred in patients operated on 23 October by the same surgeon; no additional cases were identified. P. aeruginosa was isolated from all three patients. Of 45 environmental samples, three were positive: the laundry room drain, the sink drain in the local anesthesia room, and the interior of cassette No. 2 and instruments within the operating room steam sterilizer. PFGE showed 95.7% band pattern similarity between patient isolates and those from the sterilizer. This outbreak was attributed to P. aeruginosa, with the steam sterilizer identified as the most probable source. Inadequate infection control and sterilization practices likely contributed. These findings highlight the critical importance of strict sterilization monitoring and adherence to infection prevention and control practices to prevent recurrence. Full article

(This article belongs to the Special Issue Advances in the Epidemiology of Human Infectious Diseases)

14 pages, 24898 KB

Open AccessArticle

Antifungal Effects of Citrus maxima Cultivar Tubtim-Siam Peel Extract Against Malassezia pachydermatis Isolated from Dogs

by Watcharapong Mitsuwan, Juthatip Jeenkeawpieam, Ratchadaporn Boripun, Noppharat Tanthanathipchai, Ozioma Forstinus Nwabor and Phirabhat Saengsawang

Pathogens 2026, 15(5), 479; https://doi.org/10.3390/pathogens15050479 - 29 Apr 2026

Abstract

Otitis externa in dogs is primarily caused by Malassezia pachydermatis. Treatment involves antifungal and antiseptic agents; however, resistance among causative organisms has been noted. Pomelo (Citrus maxima) is a source of bioactive compounds with antimicrobial activity. Its extract mainly includes [...] Read more.

Otitis externa in dogs is primarily caused by Malassezia pachydermatis. Treatment involves antifungal and antiseptic agents; however, resistance among causative organisms has been noted. Pomelo (Citrus maxima) is a source of bioactive compounds with antimicrobial activity. Its extract mainly includes essential oils, which are mostly applied for alternative treatment for M. pachydermatis. The study aimed to investigate the anti-M. pachydermatis effects of pomelo peel extracts and their potential use in topical solutions for canine infections. M. pachydermatis was isolated from dogs and confirmed with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF/MS). Antifungal susceptibility of M. pachydermatis to itraconazole was evaluated. Phytochemicals of essential oil and crude extract from C. maxima peel were determined using Gas Chromatograph–Mass Spectrometry (GC-MS/MS). In addition, the antifungal activity of the extracts was assessed using an agar plate dilution assay. The essential oil was formulated into a prototypic topical solution, and its effects on M. pachydermatis were observed in vitro. The prevalence of M. pachydermatis was 42%, with 53% having yeast on both ear sides. The minimum inhibitory concentrations (MIC) of itraconazole, essential oil, and crude extract to M. pachydermatis were 0.03–0.25 µg/mL, 1.0% v/v, and >200 mg/mL, respectively. The prominent phytochemicals in peel extracts were meranzin hydrate and D-limonene, identified in the crude extract and essential oil, respectively. Moreover, a topical solution containing essential oils inhibited M. pachydermatis growth and showed destructive effects on the yeast cell wall at higher concentrations. The essential oil exhibits antifungal activity against M. pachydermatis, primarily due to the high concentration of D-limonene. The growth was inhibited completely at MIC, observed over a 5-day period. Furthermore, the prototypic topical solution demonstrated an anti-M. pachydermatis effect. These findings suggest potential veterinary applications for pomelo peel extract, though further studies are necessary to assess stability, mechanism of action, and industrial suitability. Full article

(This article belongs to the Special Issue Fighting Pathogens with Natural Antimicrobials)

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17 pages, 1371 KB

Open AccessArticle

Growth Enhancement of Salmonella by Tungstate Treatment

by Robin C. Anderson, Delila D. Dominguez, Megan R. Shaw, Casey N. Johnson, Samat Amat, Jackie M. Kotzur, Merritt L. Drewery, Patricia J. Baynham, Ken J. Genovese, Tawni L. Crippen and Ryan J. Arsenault

Pathogens 2026, 15(5), 478; https://doi.org/10.3390/pathogens15050478 - 29 Apr 2026

Abstract

Salmonella in gut habitats have traditionally been thought to conserve energy for growth via fermentation. However, recent reports indicate that ingested Salmonella can stimulate host-derived nitrate accumulation in the mucosal microenvironment, thereby enabling growth through nitrate respiration. Sodium tungstate is an effective treatment [...] Read more.

Salmonella in gut habitats have traditionally been thought to conserve energy for growth via fermentation. However, recent reports indicate that ingested Salmonella can stimulate host-derived nitrate accumulation in the mucosal microenvironment, thereby enabling growth through nitrate respiration. Sodium tungstate is an effective treatment that inhibits the growth of certain nitrate-respiring bacteria, including Escherichia coli, Paracoccus and Proteus, when cultured under gut simulating conditions or within the gut of experimentally treated mice. This inhibitory effect is hypothesized to occur by inactivation of molybdenum-containing enzymes required for nitrate metabolism. Information is lacking on whether tungstate can inhibit the growth of Salmonella, particularly in the presence of culturable gut microbiota. Therefore, the objectives of this study were to evaluate the effects of sodium tungstate on Salmonella during pure culture or when cultured with freshly collected bovine rumen microbiota and to assess its impact on fermentation as well as nitrate and nitrite metabolism within the rumen microbial cultures. Our results indicate that 50 mM sodium tungstate treatment, whether alone or in combination with 5 mM nitrate, markedly increased the growth of Salmonella serovars Newport, Dublin and Typhimurium during pure culture. Moreover, during in vitro incubation, increased growth of experimentally inoculated S. Newport as well as wildtype E. coli and lactic acid bacteria was observed with ruminal microbiota treated with 100 mM tungstate when compared to non-tungstate-treated controls. Effects of tungstate on nitrate and nitrite metabolism were as expected during pure and mixed culture. When cultured with reduced tungsten rather than tungstate, the latter being bound to four oxygen atoms, an inhibitory effect on the growth of S. Newport was observed and effects on nitrate and nitrite metabolism were consistent with those observed with tungstate. These results suggest that, under conditions used in the present experiments, tungstate may have served as a source of oxygen for respiration above that achieved with nitrate alone. While this hypothesis has yet to be proven, it is supported by an adverse effect of tungstate, whether alone or in combination with 5 mM nitrate, on methane and volatile fatty acid production by the ruminal microbiota when compared to untreated or nitrate-only-treated microbiota. Full article

(This article belongs to the Special Issue Zoonotic Salmonella Infections: Transmission Dynamics and Control)

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13 pages, 1076 KB

Open AccessReview

Russian Dolls of Heme Metabolism in Malaria-Infected Red Blood Cells: Nested Vulnerabilities and Therapeutic Opportunities

by Swamy R. Adapa, Faiza A. Siddiqui and Rays H. Y. Jiang

Pathogens 2026, 15(5), 477; https://doi.org/10.3390/pathogens15050477 - 29 Apr 2026

Abstract

Heme metabolism is central to the biology of malaria parasites and to the mechanism of action of artemisinin-based therapies. Within malaria-infected red blood cells (RBCs), heme-related chemistry arises from multiple nested metabolic sources that function as “Russian dolls”: the truncated heme biosynthetic capacity [...] Read more.

Heme metabolism is central to the biology of malaria parasites and to the mechanism of action of artemisinin-based therapies. Within malaria-infected red blood cells (RBCs), heme-related chemistry arises from multiple nested metabolic sources that function as “Russian dolls”: the truncated heme biosynthetic capacity of the host erythrocyte, the parasite’s own heme synthesis pathway, and host heme released through hemoglobin digestion in the parasite food vacuole. These overlapping metabolic layers create distinct pools of heme that can influence redox balance and drug activation. Recent studies highlight that exogenous 5-aminolevulinic acid (5-ALA) can perturb host heme biosynthesis in infected erythrocytes, potentially increasing intracellular levels of the heme intermediate protoporphyrin IX and sensitizing parasites to oxidative stress. However, the extent to which such metabolic perturbations affect artemisinin susceptibility depends strongly on parasite stage and exposure duration. Here we review the compartmentalized architecture of heme metabolism in malaria-infected RBCs and discuss how these nested vulnerabilities may be exploited for therapeutic intervention. Full article

(This article belongs to the Special Issue Discovery of Novel Antiprotozoal Agents: Current Status and Future Perspectives)

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16 pages, 4637 KB

Open AccessArticle

Two Multidrug-Resistant Escherichia coli Isolates from Blood Cultures After Cervical Conization in a Patient with Cervical Intraepithelial Neoplasia Grade II: Phenotypic and Genomic Characterization

by Jingrui Zhang, Xiao Liu, Li Liu, Yeshun Fan, Zhiwen Sun, Mengjie Li, Yanwen Xiong, Zengbin Liu, Yanfang Li, Lili Yu, Hongru Feng, Duochun Wang and Jingxiao Zhang

Pathogens 2026, 15(5), 476; https://doi.org/10.3390/pathogens15050476 - 28 Apr 2026

Abstract

Patients undergoing cervical conization for cervical intraepithelial neoplasia grade II (CIN II) may develop postoperative bloodstream infections (BSIs), and multidrug-resistant (MDR) Escherichia coli isolates with distinct resistance profiles can complicate antimicrobial management. In this case-based study, two E. coli strains, HBFY-1 and HBFY-2, [...] Read more.

Patients undergoing cervical conization for cervical intraepithelial neoplasia grade II (CIN II) may develop postoperative bloodstream infections (BSIs), and multidrug-resistant (MDR) Escherichia coli isolates with distinct resistance profiles can complicate antimicrobial management. In this case-based study, two E. coli strains, HBFY-1 and HBFY-2, were recovered from blood cultures obtained from a 38-year-old CIN II patient with postoperative fever. The isolates were characterized by antimicrobial susceptibility testing, whole-genome sequencing, conjugation assays, and comparative genomics against publicly available genomes matched by sequence type and serotype. Fever occurred on postoperative day 2. HBFY-1 was fluoroquinolone-resistant; belonged to ST744/O101:H9; carried the extended-spectrum β-lactamase (ESBL) gene bla_CTX-M-27; was phenotypically confirmed as an ESBL producer; and grouped within a multi-source near-neighbor clade consistent with a conserved fluoroquinolone-associated resistance backbone in ST744/O101:H9. HBFY-2 was carbapenem-resistant; belonged to ST48/O113:H32; carried bla_NDM-5 on an IncY-associated plasmid bin; was phenotypically confirmed as a metallo-carbapenemase producer; and did not harbor any ESBL gene. Within the matched ST48/O113:H32 dataset, bla_NDM-5 was detected only in HBFY-2, which clustered within an Asia-enriched lineage, including China-derived human and swine genomes. The bla_CTX-M-27-associated and bla_NDM-5-associated elements were transferred to E. coli C600 at frequencies of 5.3 × 10⁻² and 4.6 × 10⁻⁶, respectively, and transfer of the bla_NDM-5-associated element imposed no detectable growth penalty under the tested conditions. As this study is based on a single clinical case, the findings should be interpreted cautiously, yet they still highlight the potential value of integrating susceptibility testing with rapid genomic characterization for identifying mobilizable carbapenem-resistance platforms. Full article

(This article belongs to the Section Bacterial Pathogens)

11 pages, 452 KB

Open AccessArticle

New Findings on the Hosts and Distribution of Eustrongylides excisus (Nematoda: Dioctophymatidae) and Other Zoonotic Parasites in Fish Species from an Uninvestigated Subalpine Lake, Varese Lake (Northwestern Italy)

by Michele Macrelli, Martina Ossola, Giovanni Sala, Damiano Accurso, Monica Caffara, Andrea Gustinelli, Marco Farioli and Cristian Salogni

Pathogens 2026, 15(5), 475; https://doi.org/10.3390/pathogens15050475 - 28 Apr 2026

Abstract

The increasing consumption of fish has raised public health concerns regarding fish-borne zoonotic helminths (FBZHs), which are recognized as significant food-borne parasites worldwide. In freshwater environments, Clinostomum complanatum, Opisthorchis felineus, Pseudamphistomum truncatum, Dibothriocephalus latus and Eustrongylides excisus are of particular [...] Read more.

The increasing consumption of fish has raised public health concerns regarding fish-borne zoonotic helminths (FBZHs), which are recognized as significant food-borne parasites worldwide. In freshwater environments, Clinostomum complanatum, Opisthorchis felineus, Pseudamphistomum truncatum, Dibothriocephalus latus and Eustrongylides excisus are of particular concern in Italy and neighbouring countries. This study aimed to assess the prevalence of these FBZHs in five commercially and ecologically relevant freshwater fish species from Lake Varese, a heavily anthropized and understudied basin in northern Italy. A total of 59 fish were examined via necropsy and stereomicroscopic inspection of skeletal muscles. Only Eustrongylides spp. larvae were detected, with a prevalence of 16.9%. Molecular analysis (ITS region) identified them as E. excisus. This study reports, for the first time in Western Europe, E. excisus in Sander lucioperca (p = 12.5%) and Esox lucius (p = 8.3%). The highest prevalence occurred in Silurus glanis (p = 37.5%), followed by Perca fluviatilis (p = 25.0%), while Tinca tinca showed no infection. These findings confirm that among the FBZHs considered, E. excisus is currently present and expanding both in host range and geography in Italian lakes, underscoring the need for updated epidemiological data to support risk assessment, food safety and zoonotic parasite control in freshwater fisheries. Full article

(This article belongs to the Section Parasitic Pathogens)

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