Pathogens

22 pages, 2589 KB

Open AccessArticle

Early Platelet Dysfunction in Sepsis: An ICU Pilot Study

by Maria Grazia Bocci, Silvia Sorrentino, Ilaria Gatto, Daniele Natalini, Emiliano Cingolani, Allegra Blandina, Francesca Botta, Manfred Caravella, Simone Carelli, Domenico Luca Grieco, Alessandra Ionescu Maddalena, Luca D’Innocenzo, Matteo De Siati, Riccardo Maviglia, Chiara Gori and Erica De Candia

Pathogens 2026, 15(2), 196; https://doi.org/10.3390/pathogens15020196 - 10 Feb 2026

Abstract

Platelets are critical for hemostasis and play an active role in immune responses to infection. While thrombocytopenia in sepsis is associated with poor outcomes, platelet dysfunction remains less explored. This prospective observational pilot study investigated the relationship between platelet dysfunction and sepsis severity [...] Read more.

Platelets are critical for hemostasis and play an active role in immune responses to infection. While thrombocytopenia in sepsis is associated with poor outcomes, platelet dysfunction remains less explored. This prospective observational pilot study investigated the relationship between platelet dysfunction and sepsis severity using multiple platelet function tests. Ten adults with sepsis or septic shock admitted to the ICU of “Fondazione Policlinico Universitario A. Gemelli” and seven healthy controls were enrolled. Blood samples were collected at admission (T0), after 48 h (T1), and after 7 days (T2). Controls were sampled only at T0. Besides platelet count, hemostatic platelet function was assessed by light transmission aggregometry (LTA), thromboelastography (TEG), and platelet activation markers (P-selectin and PAC-1 expression), whereas immune platelet function was assessed by investigation of platelet–leukocyte aggregates and soluble plasma levels of CD40L. Platelet function was correlated with procalcitonin levels and SOFA scores. While thrombocytopenia developed after 48 h, hemostatic and immune platelet dysfunctions were already evident at T0. Platelet function abnormalities were correlated with sepsis severity, as reflected by higher SOFA scores and elevated procalcitonin levels, particularly at T0. Early platelet dysfunction, preceding thrombocytopenia, may represent a potential early indicator of sepsis severity and support timely intervention for hemostatic and immune platelet-dependent abnormalities in septic patients. Full article

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11 pages, 433 KB

Open AccessArticle

Clinical and Microbiological Profile of Oral Candidiasis: A Retrospective Study

by Maja Ptasiewicz, Karolina Thum-Tyzo, Alicja Matejko, Julia Georges, Emanuela Bis, Aleksandra Strączek, Renata Chałas and Agnieszka Magryś

Pathogens 2026, 15(2), 195; https://doi.org/10.3390/pathogens15020195 - 10 Feb 2026

Abstract

Introduction: Oral candidiasis is a common opportunistic fungal infection of the oral mucosa, most frequently caused by Candida albicans. Its development is influenced by local factors, such as denture use and oral hygiene, as well as systemic conditions including diabetes, nutritional [...] Read more.

Introduction: Oral candidiasis is a common opportunistic fungal infection of the oral mucosa, most frequently caused by Candida albicans. Its development is influenced by local factors, such as denture use and oral hygiene, as well as systemic conditions including diabetes, nutritional deficiencies, and chronic inflammatory diseases. Accurate diagnosis requires both clinical evaluation and mycological testing. The aim of this retrospective study was to analyze demographic characteristics, predisposing factors, and the species distribution of Candida isolates in patients diagnosed with oral candidiasis. Materials and Methods: A retrospective review of medical documentation was conducted to evaluate patient demographics, risk factors, comorbidities, denture use, and results of mycological examinations confirming oral candidiasis. Results: A total of 71 patients (49 women and 22 men), aged 21–85 years (mean 59.6 ± 16 years), were included in the study. Fungal etiology was confirmed in all cases, with Candida albicans identified most frequently (81.69%). Among comorbidities, cardiovascular diseases were most common (30.99%), followed by diabetes (14.08%), and chronic periodontitis, respiratory, and gastrointestinal diseases (each 11.27%). Removable dentures were used by 18.30% of patients, and nicotine addiction was reported in 9.86%. All strains were susceptible to the tested antifungals, except for species with known intrinsic resistance. Conclusions: Oral candidiasis in this cohort predominantly affected women and older adults, with Candida albicans remaining the most common etiological agent. Denture use emerged as an important local predisposing factor and was associated with a higher proportion of infections caused by non-albicans species. These findings underscore the importance of comprehensive clinical evaluation and routine mycological testing to guide targeted antifungal therapy, especially in patients with risk factors such as denture use or systemic comorbidities. Full article

(This article belongs to the Special Issue Insights into Fungal Infections)

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26 pages, 1268 KB

Open AccessReview

Berberine Interferes with the Molecular Landscape of Biofilm-Driven Pathogenicity

by Anna Duda-Madej, Hanna Bazan, Jakub Łabaz and Szymon Viscardi

Pathogens 2026, 15(2), 194; https://doi.org/10.3390/pathogens15020194 - 10 Feb 2026

Abstract

Biofilm-associated infections pose a significant clinical challenge due to their increased antibiotic tolerance and strong association with multidrug-resistant pathogens. The biofilm protects bacteria against antimicrobial agents and host immune response through a complex matrix, altered cell metabolism, activation of quorum sensing, and overexpression [...] Read more.

Biofilm-associated infections pose a significant clinical challenge due to their increased antibiotic tolerance and strong association with multidrug-resistant pathogens. The biofilm protects bacteria against antimicrobial agents and host immune response through a complex matrix, altered cell metabolism, activation of quorum sensing, and overexpression of efflux pumps. Despite the availability of numerous therapeutic strategies, the effectiveness of treatment of these infections remains limited, justifying the search for new pharmaceutics, e.g., compounds of natural origin. Berberine, an isoquinoline alkaloid from the plants of the Berberidaceae family, is of growing interest due to its broad spectrum of antimicrobial and antibiofilm activities. This review summarizes the current state of knowledge regarding the molecular mechanisms of action of berberine against the biofilm forming Gram-(+) and Gram-(−) bacteria. Its effect on bacterial cell adhesion, modulation of quorum sensing, inhibition of extracellular matrix synthesis, disruption of biofilm maturation, and the dispersion process are discussed. The role of berberine as an adjuvant to antibiotic therapy was also analyzed, in particular, its ability to restore bacterial sensitivity to different classes of antibiotics. The pharmacokinetic limitations of berberine and the prospects for the use of modern delivery systems are also considered. The collected data indicate that berberine is a promising factor supporting the treatment of biofilm-related infections. Full article

(This article belongs to the Special Issue From Whisper to Resistance: Bacterial Dialogues Behind Biofilm)

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15 pages, 1751 KB

Open AccessArticle

Chewing Lice (Phthiraptera: Amblycera, Ischnocera) of the Common Buzzards (Buteo buteo) in Romania: Host Age and Habitat Jointly Determine Lice Infestation

by Călin Mircea Gherman, Gianluca D’Amico, Katarzyna Anna Hołówka, Florinel Gheorghe Brudaşcă, Petru Burduhos, Alexandru Bulacu, Dan-Traian Ionescu, Sándor Hornok and Attila D. Sándor

Pathogens 2026, 15(2), 193; https://doi.org/10.3390/pathogens15020193 - 10 Feb 2026

Abstract

(1) Background: The common buzzard (Buteo buteo) is the most widespread raptor in Romania. This study aimed to assess the occurrence of chewing louse species and the factors influencing the epidemiology of louse infestation in the national bird populations. (2) Methods: [...] Read more.

(1) Background: The common buzzard (Buteo buteo) is the most widespread raptor in Romania. This study aimed to assess the occurrence of chewing louse species and the factors influencing the epidemiology of louse infestation in the national bird populations. (2) Methods: Between 2012 and 2025, a total of 131 buzzards were collected from all over Romania, which were either roadkilled or died due to health issues. These birds were parasitologically examined, the gathered lice were identified, and epidemiological parameters were determined. (3) Results: The overall prevalence of louse infestation was 77.9%, with 4389 specimens collected. Five species were identified: Degeeriella fulva (55.7%), Craspedorrhynchus platystomus (37.4%), Colpocephalum nanum (42.0%), Colpocephalum turbinatum (7.6%), and Laemobothrion maximum (2.3%). Among the factors influencing the evolution of louse infestations, birds’ age statistically significantly affected only the mean intensity (48.0 in subadults and 28.6 in adults, p < 0.001). Combined origin and season through temperatures and relative humidity also influenced the mean intensity of infestations. Sex-ratio and nymph-to-female ratio were, in the majority, female-biased and nymph-biased. (4) Conclusions: Lice infestation patterns of common buzzards are shaped more commonly by environmental and biogeographic context than by host sex, with temperature, humidity gradients, and region of origin primarily influencing mean intensity rather than prevalence. In addition, sex ratios were consistently female-biased across all lice species, and nymph-to-female ratios suggested contrasting demographic trajectories among taxa, with evidence of expanding infrapopulations in some species and more senescent structures in others. Full article

(This article belongs to the Special Issue Advancements in Host-Parasite Interactions)

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11 pages, 724 KB

Open AccessArticle

An Evaluation of IL-10 Encoded by Cytomegalovirus in the Prediction of Coronary Artery Disease in People Living with HIV

by Shelley Waters, Luna-Faye Veld, Silvia Lee, Anna C. Hearps, Janine Trevillyan, Jennifer F. Hoy and Patricia Price

Pathogens 2026, 15(2), 192; https://doi.org/10.3390/pathogens15020192 - 9 Feb 2026

Abstract

Cytomegalovirus (CMV) seropositivity associates with cardiovascular disease in healthy adults, but associations are unclear in people living with HIV (PLWH) despite their high CMV burden. However, CMV antibody levels correlated with inflammatory biomarkers only in PLWH who subsequently developed coronary artery disease (CAD), [...] Read more.

Cytomegalovirus (CMV) seropositivity associates with cardiovascular disease in healthy adults, but associations are unclear in people living with HIV (PLWH) despite their high CMV burden. However, CMV antibody levels correlated with inflammatory biomarkers only in PLWH who subsequently developed coronary artery disease (CAD), so the effects of CMV in an individual may vary. Here we investigate the role of CMV-encoded interleukin-10 (cmvIL-10) in PLWH on anti-retroviral therapy. Plasma levels of cmvIL-10 and antibodies reactive with a cmvIL-10 peptide or a lysate of CMV-infected fibroblasts were assessed in PLWH with or without CAD. cmvIL-10 was assessed at diagnosis/selection (T0) and 12 months earlier (T-12), with anti-cmvIL-10 also assessed at −24 and −36 months (n = 36–58/group). Plasma cmvIL-10 was recorded as positive in 5–10 PLWH per group, irrespective of CAD status. Of 21 PLWH with detectable cmvIL-10, only six were positive at both timepoints. Anti-cmvIL-10 was measurable in all samples, at levels independent of cmvIL-10, CAD or time of sampling. Amongst PLWH without CAD, the detection of cmvIL-10 associated with higher levels of CXCL10 (T0 and T-12) and lower levels of the IL-1 receptor antagonist (IL-1Ra; T0 only). At T-12, anti-cmvIL-10 correlated with IL-1Ra in PLWH without CAD (p = 0.01), and sCD14 in PLWH with CAD (p = 0.01). Anti-cmvIL-10 correlated with VCAM-1 at several timepoints in both groups. Hence, cmvIL-10 may be produced episodically, inducing anti-cmvIL-10 peptide antibody, which may represent levels of the cytokine averaged over time. Plasma levels of cmvIL-10 and anti-cmvIL-10 antibody associated differently with inflammatory biomarkers in PLWH with and without CAD, suggesting mechanisms by which host responses to CMV may have different clinical consequences. Full article

(This article belongs to the Special Issue Human Cytomegalovirus: From Molecular Pathogenesis to Therapeutic Innovations)

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Graphical abstract

12 pages, 1011 KB

Open AccessArticle

Integrating MALDI-TOF Mass Spectrometry and Machine Learning for Rapid and Clinically Relevant Differentiation of MRSA and MSSA

by Abdurrahman Gülmez, Ayşe Nur Ceylan, Selda Kömeç, Beyza Öncel and Yasin Sağlam

Pathogens 2026, 15(2), 191; https://doi.org/10.3390/pathogens15020191 - 9 Feb 2026

Abstract

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is routinely used in clinical microbiology for rapid species identification; however, its potential to support early antimicrobial decision-making remains under active investigation. Rapid discrimination of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) at [...] Read more.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is routinely used in clinical microbiology for rapid species identification; however, its potential to support early antimicrobial decision-making remains under active investigation. Rapid discrimination of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) at the time of identification could facilitate earlier optimization of antimicrobial therapy and infection control measures. In this study, MALDI-TOF MS spectral data were analyzed to evaluate supervised machine learning–based differentiation of MRSA and MSSA. A total of 91 S. aureus isolates (37 MRSA and 54 MSSA) were included, with methicillin susceptibility determined by the cefoxitin disk diffusion test according to EUCAST guidelines and used as the reference standard. MALDI-TOF MS spectra were acquired following standard on-plate extraction, subjected to quality control, and preprocessed prior to analysis. Principal component analysis demonstrated partial but consistent separation between MRSA and MSSA isolates. A Random Forest classifier was trained and validated using stratified 10-fold cross-validation, achieving an overall classification accuracy of 81.3% and a receiver operating characteristic area under the curve of 0.916. Class-specific analysis revealed high precision for MRSA (95.5%) and excellent recall for MSSA (98.1%). These findings indicate that MALDI-TOF MS combined with machine learning can provide clinically relevant information for rapid MRSA/MSSA differentiation and may serve as a cost-free decision-support approach in routine clinical microbiology workflows, complementing standard phenotypic susceptibility testing. Full article

(This article belongs to the Section Bacterial Pathogens)

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21 pages, 4069 KB

Open AccessReview

Epidemiological Characteristics of Dengue Disease in Mexico (2014–2025): A Descriptive Analysis of a Hyperendemic Country

by Rosa Cremades, Elena Sandoval-Pinto, Ana Maria Ortega-Prieto, Jose M. Jimenez-Guardeño, Héctor Raúl Pérez-Gómez, Juan Carlos Lona Reyes, Erick Sierra-Díaz and Jose Angel Regla-Nava

Pathogens 2026, 15(2), 190; https://doi.org/10.3390/pathogens15020190 - 8 Feb 2026

Abstract

Dengue is considered the most prevalent mosquito-borne arboviral disease worldwide, representing a public health challenge as its incidence has tripled in the last 30 years. The World Health Organization reports 390 million infections annually in more than 129 countries, with approximately 96 million [...] Read more.

Dengue is considered the most prevalent mosquito-borne arboviral disease worldwide, representing a public health challenge as its incidence has tripled in the last 30 years. The World Health Organization reports 390 million infections annually in more than 129 countries, with approximately 96 million symptomatic cases and around 40,000 deaths. Mexico is a hyperendemic country, with high prevalence and significant outbreaks. In 2024, a surge was observed, with approximately 125,000 infections and nearly 480 deaths. The states with the most cases and deaths were Colima and Jalisco, respectively, placing significant strain on healthcare services and driving up costs. The disease’s epidemiology from 2014 to 2025 is characterized by marked seasonality and periodicity, and by the simultaneous circulation of all four serotypes. In recent years, a notable increase in DENV-3 has been observed. In 2025, there were 21,981 confirmed cases; Sonora recorded the highest incidence, while Jalisco and Sinaloa reported the highest number of deaths. This study provides a unique decadal analysis of the epidemiological characteristics of dengue in Mexico, highlighting potential challenges and emphasizing the importance of epidemiological surveillance and future approaches, such as vaccine provision in the country, to mitigate the high mortality rate and associated costs. Full article

(This article belongs to the Special Issue Understanding Emerging and Re-Emerging Viral Infections)

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19 pages, 2903 KB

Open AccessArticle

Integrated FTIR and Whole-Genome Sequencing Reveal Scale-Dependent Genotype–Phenotype Relationships in Multidrug-Resistant Pseudomonas aeruginosa

by György Lengyel, Eszter Kaszab, Enikő Fehér, Szilvia Marton, László Orosz, Ágnes Sarkadi-Nagy, Katalin Burián and Krisztián Bányai

Pathogens 2026, 15(2), 189; https://doi.org/10.3390/pathogens15020189 - 8 Feb 2026

Abstract

Multidrug-resistant Pseudomonas aeruginosa is a major cause of healthcare-associated infections, particularly in high-burden clinical settings where rapid tools to capture clinically relevant resistance and virulence phenotypes are needed. In this study, we applied an integrated whole-genome sequencing (WGS) and Fourier-transform infrared (FTIR) spectroscopy [...] Read more.

Multidrug-resistant Pseudomonas aeruginosa is a major cause of healthcare-associated infections, particularly in high-burden clinical settings where rapid tools to capture clinically relevant resistance and virulence phenotypes are needed. In this study, we applied an integrated whole-genome sequencing (WGS) and Fourier-transform infrared (FTIR) spectroscopy approach to evaluate genotype–phenotype relationships in multidrug-resistant P. aeruginosa isolates collected during the COVID-19 pandemic. High-quality WGS data were used to characterize antimicrobial resistance determinants, mobile genetic elements, and virulence gene repertoires, while FTIR spectroscopy provided culture-based phenotypic fingerprints reflecting cell envelope composition. Genomic analyses revealed a conserved efflux-centered intrinsic resistance backbone, variably supplemented by acquired β-lactamases and aminoglycoside-modifying enzymes, alongside a largely conserved core virulome with heterogeneity driven primarily by type III secretion system effector profiles. Comparison of FTIR- and WGS-derived distance matrices revealed a weak but statistically significant global association, indicating a non-linear relationship between genomic relatedness and phenotypic similarity. Cluster-level concordance was strongly scale-dependent, with high agreement emerging only at finer clustering resolutions, consistent with FTIR capturing phenotypic variation linked to regulatory, metabolic, and cell envelope adaptations rather than deep phylogenetic structure. Together, these findings show that multidrug resistance and virulence in P. aeruginosa are shaped by a modular genomic architecture that manifests as distinct, measurable phenotypic states. The observed scale-dependent concordance supports FTIR spectroscopy as a rapid, cost-effective phenotypic screening tool for outbreak-oriented surveillance, complementing WGS in integrated antimicrobial resistance monitoring workflows. Full article

(This article belongs to the Section Bacterial Pathogens)

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11 pages, 4105 KB

Open AccessBrief Report

Elevated Antibacterial Activity of a Polygalacturonic + Caprylic Acids Wound Ointment Compared with Hypochlorous Acid in a Three-Dimensional Wound Biofilm Model

by Bahgat Gerges, Joel Rosenblatt, Y-Lan Truong, Ying Jiang and Issam Raad

Pathogens 2026, 15(2), 188; https://doi.org/10.3390/pathogens15020188 - 8 Feb 2026

Abstract

Bacterial biofilms play a major role in delayed wound-healing and in the development of chronic, non-healing wounds. Natural, plant-based agents, which can eradicate bacterial biofilms, are alternatives to antibiotics and antiseptics in the treatment of bacterially contaminated wounds. Bacterial wound biofilms are three-dimensional [...] Read more.

Bacterial biofilms play a major role in delayed wound-healing and in the development of chronic, non-healing wounds. Natural, plant-based agents, which can eradicate bacterial biofilms, are alternatives to antibiotics and antiseptics in the treatment of bacterially contaminated wounds. Bacterial wound biofilms are three-dimensional and complex microbial communities. Therefore, in this study, we used a three-dimensional fibrin-gel wound biofilm (FGWB) model to compare a commonly used natural agent in wound care, hypochlorous acid (HOCl), to a combination of two natural plant-based agents, polygalacturonic acid (PG) and caprylic acid (CAP) (PG + CAP), for their abilities to eradicate resistant bacterial biofilms of common wound pathogens methicillin resistant Staphylococcus aureus (MRSA), multi-drug resistant (MDR) Pseudomonas aeruginosa, metallo β-Lactamase Escherichia coli, and Streptococcus pyogenes. PG + CAP produced a significantly greater reduction in viable organisms when compared to HOCL (p ≤ 0.05) against all tested bacterial isolates. PG + CAP was highly effective against biofilms of all resistant bacterial isolates and is a promising option that merits further study for treating chronic wounds contaminated with bacterial biofilms. Full article

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

12 pages, 3268 KB

Open AccessArticle

Single Isothermal Assay for Multi-Site Mutation Detection of Rifampicin Resistance in Mycobacterium tuberculosis

by Nidhi Nandu, Michael Miller and Zhi-xiang Lu

Pathogens 2026, 15(2), 187; https://doi.org/10.3390/pathogens15020187 - 8 Feb 2026

Abstract

Antimicrobial drug resistance is an escalating global health burden, often driven by multiple genetic changes within key resistance-associated genes. Achieving multiplex capability of mutation detection while maintaining simplicity and affordability is critical, particularly in point-of-care and resource-limited settings. Here, we introduce a strategy [...] Read more.

Antimicrobial drug resistance is an escalating global health burden, often driven by multiple genetic changes within key resistance-associated genes. Achieving multiplex capability of mutation detection while maintaining simplicity and affordability is critical, particularly in point-of-care and resource-limited settings. Here, we introduce a strategy for multi-site mutation detection using single isothermal amplification of a nucleic acid fragment spanning multiple mutations in the rifampicin resistance-determining region (RRDR) of the rpoB gene, encompassing codons 516 and 526 in Mycobacterium tuberculosis. This unified design eliminates competition among targets amplified by multiple primer sets. Site-specific hybridization probes enable accurate discrimination between wild-type and mutant sequences, while an integrated self-calibration probe provides normalization to mitigate variability from sample concentration and sample matrix interference. To validate this approach, we applied it to detect rifampicin (RIF) resistance mutations at codons 516 and 526 of the rpoB gene in Mycobacterium tuberculosis, which are two key targets for molecular diagnostics and surveillance. Using 42 artificial DNA fragments, which included both wild-types and mutants with single- or two-site mutations, the assay achieved 100% accuracy in discriminating between wild-type and mutant sequences for codon 516. On the other hand, sequences harboring mutations at codon 526 were identified with 100% accuracy, compared to 94% accuracy for wild-type sequences. Overall, the system achieved a 100% positive percent agreement (PPA) for drug-resistance sequences and 97% negative percent agreement (NPA) for drug-sensitive sequences based on these 42 samples. These findings suggest that this method has the potential to provide a reliable framework for multi-site mutation detection. Full article

(This article belongs to the Section Bacterial Pathogens)

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27 pages, 1142 KB

Open AccessReview

Molecular Pathways Driving Corneal Neovascularization in Herpes Simplex Keratitis

by Soromidayo Akinsiku and Deepak Shukla

Pathogens 2026, 15(2), 186; https://doi.org/10.3390/pathogens15020186 - 7 Feb 2026

Abstract

Herpes simplex keratitis (HSK) is classically described as an immunopathological disease driven by recurrent herpes simplex virus type 1 (HSV-1) infection and chronic inflammation. So far, immune-mediated tissue damage has not fully explained the molecular mechanisms governing disease progression toward corneal neovascularization (CNV), [...] Read more.

Herpes simplex keratitis (HSK) is classically described as an immunopathological disease driven by recurrent herpes simplex virus type 1 (HSV-1) infection and chronic inflammation. So far, immune-mediated tissue damage has not fully explained the molecular mechanisms governing disease progression toward corneal neovascularization (CNV), a major cause of corneal blindness and vision loss worldwide. Increasing evidence indicates that CNV results from complex interactions that extend beyond leukocyte-driven inflammation, as the host cell machinery, including key pathways and molecular markers, is hijacked by the invading virus to establish and perpetuate replication and lifelong latency. These host–cell interactions regulate angiogenic imbalance, vascular privilege, and tissue remodeling, which collectively promote pathological vascular invasion. This review re-examines HSK by focusing on molecular mechanistic pathways and drivers that regulate disease progression towards CNV, upstream of immune response drivers. Specifically, we discuss the roles of endothelial growth factors, matrix metalloproteinases, Heparanase, and Syndecan-1 signaling, as well as microRNA-mediated regulation, and key signaling axes, including JAK2/STAT3, PI3K/AKT/mTOR, and hypoxia signaling. By integrating these pathways and molecular markers, we propose an updated mechanistic framework, including a conceptual model for the underexplored role of heparanase, and identify pathway-level targets with potential therapeutic relevance for HSK-associated CNV. Full article

(This article belongs to the Section Viral Pathogens)

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20 pages, 2188 KB

Open AccessArticle

HTD1265 Disrupts GimC-Dependent Cellular Processes in Saccharomyces cerevisiae

by Kaori Itto-Nakama, Naoya Hosoyamada, Shinsuke Ohnuki, Fumiyuki Shirai, Minagi Mukaiyama, Hiroyuki Hirano, Hiroyuki Osada, Charles Boone, Takeo Usui, Yoko Yashiroda and Yoshikazu Ohya

Pathogens 2026, 15(2), 185; https://doi.org/10.3390/pathogens15020185 - 7 Feb 2026

Abstract

HTD1265 is a newly identified antifungal compound that displays potent activity against Candida krusei, a clinically challenging non-albicans species. To elucidate its mechanism of action, we applied an integrative phenotypic approach combining high-resolution morphological profiling, pathway inference, and genetic validation in [...] Read more.

HTD1265 is a newly identified antifungal compound that displays potent activity against Candida krusei, a clinically challenging non-albicans species. To elucidate its mechanism of action, we applied an integrative phenotypic approach combining high-resolution morphological profiling, pathway inference, and genetic validation in Saccharomyces cerevisiae. Morphological signature extraction revealed a characteristic defect in nuclear positioning upon HTD1265 treatment. Integration of nuclear positioning traits with global morphological similarity highlighted 36 genes enriched for the Gene Ontology term “tubulin complex assembly.” Consistent with this prediction, HTD1265 impaired mitotic spindle elongation without directly inhibiting tubulin polymerization. HTD1265 further induced hallmarks of GimC (prefoldin) deficiency, including aberrant chitin accumulation, actin disorganization, and nuclear mispositioning, and caused hypersensitivity in GimC subunit mutants. These converging observations suggest that HTD1265 exerts antifungal activity by disrupting GimC-dependent cellular processes rather than by directly targeting tubulin. Our findings highlight GimC-dependent cytoskeletal and cell wall regulatory processes as a critical vulnerability for fungal growth and position HTD1265 as a functional tool for dissecting this pathway. Full article

(This article belongs to the Special Issue Emerging and Rare Fungal Pathogens in a Changing World)

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10 pages, 696 KB

Open AccessBrief Report

Helicobacter pylori Neutrophil Activating Protein (HP-NAP) Enhances the Anti-Leishmanial Activity of Canine Macrophages Against Leishmania infantum

by Gaia Mazza, Federica Perego, Sara Coletta, Daniela Proverbio, Mario Milco D’Elios, Donatella Taramelli, Marina De Bernard, Fabrizio Bruschi and Nicoletta Basilico

Pathogens 2026, 15(2), 184; https://doi.org/10.3390/pathogens15020184 - 7 Feb 2026

Abstract

Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) and is linked to cases of cutaneous leishmaniasis in dogs. Dogs often develop severe systemic disease and serve as the primary reservoir of L. infantum. Although several vaccine candidates are under development, [...] Read more.

Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) and is linked to cases of cutaneous leishmaniasis in dogs. Dogs often develop severe systemic disease and serve as the primary reservoir of L. infantum. Although several vaccine candidates are under development, no vaccine for visceral leishmaniasis has been approved for human use to date. Chemotherapeutic treatment is hampered by toxicity, cost, and the emergence of parasite-resistant strains. Immunotherapy, combining chemotherapy with modulation of Th1 responses, is a promising therapeutic approach. Helicobacter pylori neutrophil-activating protein (HP-NAP), an immunomodulatory protein from Helicobacter pylori, is known to promote Th1 immune responses. A Th1 response activates macrophage promoting parasite killing, while a Th2 response favors disease progression. Macrophages are central for infection, either eliminating parasites (Th1 response) or supporting their persistence (Th2 response). IL-12 is a crucial cytokine in driving Th1 immunity and counteracting Th2 responses. We therefore investigated the role of HP-NAP in an in vitro model of L. infantum macrophage infection. Canine monocyte-derived macrophages from seven dogs were incubated with L. infantum promastigotes. More than 85% of macrophages from all donors were infected, with approximately seven amastigotes per cell. HP-NAP treatment significantly reduced all infection parameters and induced IL-12 production. Collectively, these findings suggest that HP-NAP may represent a promising candidate for adjuvant immunotherapies and vaccine development against L. infantum. Full article

(This article belongs to the Special Issue Molecular Aspects of Host-Parasite Interactions)

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12 pages, 229 KB

Open AccessArticle

Microbiological Spectrum and Antimicrobial Resistance Patterns in Hand Surgery Infections: A Monocentric Retrospective Study

by Lorenzo Drago, Fabiana Giarritiello, Deflorio Loredana, Luigi Regenburgh De La Motte, Francesca Carreras, Carmen Sommese, Giorgio Eugenio Pajardi and Luigi Triosi

Pathogens 2026, 15(2), 183; https://doi.org/10.3390/pathogens15020183 - 6 Feb 2026

Abstract

Background: Infections in hand surgery represent a clinically relevant complication, particularly in trauma-related procedures and in the presence of internal fixation devices. Data specifically addressing microbiological profiles and antimicrobial resistance patterns in hand surgery remain limited. Methods: A monocentric retrospective observational study was [...] Read more.

Background: Infections in hand surgery represent a clinically relevant complication, particularly in trauma-related procedures and in the presence of internal fixation devices. Data specifically addressing microbiological profiles and antimicrobial resistance patterns in hand surgery remain limited. Methods: A monocentric retrospective observational study was conducted, including 72 patients treated for hand surgery infections between January 2024 and June 2025. Microbiological isolates and antimicrobial susceptibility profiles were analyzed and stratified according to the clinical scenario, including trauma-related infections and infections associated with internal fixation devices. Monomicrobial and polymicrobial infections were evaluated separately. Results: Trauma-related infections accounted for 77.8% of cases, of which 64.3% were monomicrobial and 35.7% polymicrobial. Monomicrobial trauma-related infections were predominantly caused by Staphylococcus aureus, with methicillin resistance detected in 25.0% of cases. Polymicrobial trauma-related infections showed greater microbiological complexity but limited antimicrobial resistance. Infections associated with internal fixation devices represented 22.2% of cases and demonstrated a higher proportion of polymicrobial infections. Across all subgroups, no extended-spectrum beta-lactamase–producing Enterobacterales or carbapenem-resistant organisms were identified. Conclusions: This study fills an important evidence gap by characterizing pathogens and antimicrobial resistance in a dedicated hand surgery cohort, an area where published microbiological data remain limited compared with other orthopedic subspecialties. Hand surgery infections exhibit distinct microbiological and resistance profiles depending on the clinical scenario and microbial complexity. Despite frequent polymicrobial involvement, high-level antimicrobial resistance remains uncommon, supporting the value of local microbiological surveillance to guide empirical therapy. Full article

18 pages, 6013 KB

Open AccessArticle

Molecular Lineage Replacement and Shifted Seasonality of Pediatric Respiratory Syncytial Virus on Tropical Hainan Island, China, 2021–2024

by Yibo Jia, Siqi Chen, Shannan Wu, Ruoyan Peng, Yi Huang, Gaoyu Wang, Meng Chang, Meifang Xiao, Yueqing Chen, Yujuan Guo and Feifei Yin

Pathogens 2026, 15(2), 182; https://doi.org/10.3390/pathogens15020182 - 6 Feb 2026

Abstract

Respiratory syncytial virus (RSV) resurged in many regions after the relaxation of stringent non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic. Here, we characterized the epidemiological patterns and molecular evolution of RSV among pediatric inpatients with acute respiratory tract infections (ARTIs) on tropical [...] Read more.

Respiratory syncytial virus (RSV) resurged in many regions after the relaxation of stringent non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic. Here, we characterized the epidemiological patterns and molecular evolution of RSV among pediatric inpatients with acute respiratory tract infections (ARTIs) on tropical Hainan Island, China. We retrospectively analyzed 32,329 children (≤18 years) hospitalized at Hainan Women and Children’s Medical Center from January 2021 to December 2024. RSV positivity was determined using targeted next-generation sequencing. In total, 4483/32,329 (13.86%) patients were RSV-positive, with a high positivity in 2021 (20.27%, 957/4721), marked suppression in 2022 (2.03%, 106/5227) during intensive NPIs, and a rebound in 2023–2024 (15.31%, 1490/9732; 15.26%, 1930/12,649). RSV positivity was higher in boys than girls (14.42% vs. 13.00%). Seasonality shifted from a summer–autumn peak in 2021 to a spring–summer predominance in 2023–2024. Among 56 sequenced RSV-positive specimens (29 RSV-A; 27 RSV-B), all RSV-A strains belonged to genotype ON1 (lineages A.D.3 and A.D.5.2), and all RSV-B strains belonged to genotype BA9 (lineages B.D.4.1.1, B.D.E.1, and B.D.E.2). Subtype dominance transitioned from RSV-A (2021–2023; mainly A.D.3) to RSV-B in 2024 (all B.D.E.1). Lineage-specific amino-acid and predicted N-glycosylation changes were observed, including loss of the N179 site in A.D.5.2 and acquisition of N258 in B.D.E.1. These findings indicate that RSV circulation on tropical Hainan was strongly suppressed during intensive NPIs and re-established after policy relaxation, accompanied by earlier seasonal activity and clear lineage replacement, underscoring the need for sustained genomic surveillance to inform locally tailored clinical preparedness and immunization strategies. Full article

(This article belongs to the Special Issue Infectious Diseases and Tropical Infections: Epidemiology, Transmission, Treatment, and Prevention)

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16 pages, 721 KB

Open AccessReview

Early Mycobacterial Antigens in the Immunodiagnosis of Latent Tuberculosis Infection

by Aigul Utegenova, Lazzat Kassayeva, Bayan Turdalina, Aliya Baiduissenova, Ayaz Yktiyarov, Marat Dusmagambetov and Evgeni Sokurenko

Pathogens 2026, 15(2), 181; https://doi.org/10.3390/pathogens15020181 - 6 Feb 2026

Abstract

Latent tuberculosis infection (LTBI) represents a major global health concern as it constitutes the principal reservoir for future tuberculosis (TB) disease. Its identification is particularly important in Bacille Calmette–Guérin (BCG)-vaccinated populations, where cross-reactivity of purified protein derivative limits the specificity of the tuberculin [...] Read more.

Latent tuberculosis infection (LTBI) represents a major global health concern as it constitutes the principal reservoir for future tuberculosis (TB) disease. Its identification is particularly important in Bacille Calmette–Guérin (BCG)-vaccinated populations, where cross-reactivity of purified protein derivative limits the specificity of the tuberculin skin test and hampers targeted preventive therapy. Early Mycobacterium tuberculosis antigens encoded within the RD1 region, especially ESAT-6, CFP-10 and TB7.7, have enabled the development of antigen-specific interferon-gamma release assays (IGRAs) and recombinant skin tests with improved BCG-independent specificity. This narrative review integrates and critically appraises current evidence on the immunobiological properties of early and latency-associated antigens, the cellular mechanisms underlying T-cell-dependent immune reactivity, and the diagnostic performance of IGRAs and ESAT-6/CFP-10-based skin tests, rather than merely summarizing individual studies. Although these platforms rely on different assay principles (in vitro cytokine release versus in vivo delayed-type hypersensitivity), both measure antigen-specific T-cell memory and do not define the biological stage of infection or reliably distinguish latent from incipient or active TB. Across most adult populations, IGRAs demonstrate high specificity and acceptable sensitivity, whereas reduced sensitivity and higher rates of indeterminate results are observed in young children and immunocompromised individuals. ESAT-6/CFP-10-based skin tests show diagnostic accuracy comparable to IGRAs and may offer operational advantages in resource-limited settings. Latency-associated antigens and host biomarkers such as IP-10, together with multi-analyte immune signatures, represent promising avenues for improving diagnostic sensitivity and prognostic stratification but currently lack sufficient validation for routine clinical use. Overall, RD1-encoded antigens remain central to LTBI immunodiagnosis, while future research should focus on developing stage-resolving and prognostic biomarkers, optimized antigen panels, and standardized interpretive frameworks. Full article

(This article belongs to the Section Bacterial Pathogens)

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41 pages, 2609 KB

Open AccessReview

Silent Intruders: The Gut Virome in Brain Aging and Cognitive Decline

by Serena Silvestro, Angelina Midiri, Carmelo Biondo, Selene Casilli, Lucia Borrello, Sebastiana Zummo and Giuseppe Mancuso

Pathogens 2026, 15(2), 180; https://doi.org/10.3390/pathogens15020180 - 6 Feb 2026

Abstract

Recent advances in next-generation sequencing have revealed that the virome—the set of viruses residing in the gastrointestinal tract—is a fundamental yet still underexplored component of the human intestinal ecosystem. Despite the prevalence of research focused on bacterial alterations, recent findings suggest a significant [...] Read more.

Recent advances in next-generation sequencing have revealed that the virome—the set of viruses residing in the gastrointestinal tract—is a fundamental yet still underexplored component of the human intestinal ecosystem. Despite the prevalence of research focused on bacterial alterations, recent findings suggest a significant role for viral elements within the intestinal microbiota, namely latent viruses, bacteriophages and eukaryotic viruses, in influencing brain health. Alterations in the gut virome may, in particular, contribute to the processes underlying brain aging, cognitive decline, and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis (MS). This review highlights the potential of intestinal viruses to modulate gut barrier integrity, systemic immune response and neuroimmune inflammation. Such interactions could promote conditions of chronic neuroinflammation, alterations in synaptic plasticity, and neuronal vulnerability. A more comprehensive understanding of the role of the gut virome could potentially result in novel approaches to the early detection and treatment of neurocognitive disorders in adults and older individuals. Full article

(This article belongs to the Section Viral Pathogens)

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13 pages, 1425 KB

Open AccessSystematic Review

The Global Landscape of Plasmodium falciparum Drug Resistance Markers, 2005–2025: A Systematic Review and Meta-Analysis

by Felix Habarugira, Jeanne Batamuriza, Raphael Ndahimana, Jules Ndoli Minega, Mame Massar Dieng, Masceline Jenipher Mutsaka-Makuvaza, Tolessa Muleta Daba, Youssef Idaghdour and Leon Mutesa

Pathogens 2026, 15(2), 179; https://doi.org/10.3390/pathogens15020179 - 6 Feb 2026

Abstract

Malaria remains a global health threat, with Plasmodium falciparum causing most deaths, especially in sub-Saharan Africa. Although artemisinin-based therapies reduce the burden, drug-resistant parasites threaten control efforts. Mapping the distribution and evolution of molecular resistance markers is vital for evidence-based strategies. This systematic [...] Read more.

Malaria remains a global health threat, with Plasmodium falciparum causing most deaths, especially in sub-Saharan Africa. Although artemisinin-based therapies reduce the burden, drug-resistant parasites threaten control efforts. Mapping the distribution and evolution of molecular resistance markers is vital for evidence-based strategies. This systematic review mapped the global distribution, pooled prevalence, and temporal trends of key P. falciparum antimalarial resistance markers. Following the PRISMA methodology (PROSPERO: CRD4202511098991), databases (PubMed, Web of Science, Scopus, and Google Scholar) and gray sources were searched (July 2005–July 2025). Data were extracted in Rayyan, assessed via the JBI prevalence tool, and analyzed using Python v3.13 for WHO regional distribution, temporal trends, and treatment outcome trends. Of the 1972 records, 261 studies from 64 countries qualified for inclusion in this review. The pooled prevalence was highest for pfdhfr (85.7%), followed by pfcrt (78.0%), pfdhps (73.7%), pfmdr1 (60.5%), and pfk13 (45.0%). High heterogeneity (I² > 95%) and rising pfk13 since 2012 highlight emerging artemisinin resistance, while persistent pfdhfr/pfdhps mutations show that ongoing sulfadoxine–pyrimethamine (SP) pressure on P. falciparum drug resistance, decreased parasite clearance, and treatment failure remain widespread and evolving in Africa. Integrating molecular surveillance into national malaria programs is essential to guide treatment modalities and support progress toward malaria elimination. Full article

(This article belongs to the Special Issue Parasitic Diseases in the Contemporary World)

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18 pages, 883 KB

Open AccessArticle

Genotype-Specific HPV E6/E7 mRNA Triage Improves Risk Stratification and Reduces Referrals in DNA-Positive ASC-US/LSIL: A Real-World Cohort from Nordland, Norway

by Khalid Al-Shibli, Dat Tan Nguyen, Hiba Abdul Latif Mohammed and Sveinung Wergeland Sørbye

Pathogens 2026, 15(2), 178; https://doi.org/10.3390/pathogens15020178 - 6 Feb 2026

Abstract

HPV DNA–positive women with ASC-US/LSIL cytology represent a heterogeneous risk group in cervical screening and require efficient triage. We evaluated a genotype-specific 7-type HPV E6/E7 mRNA assay (PreTect HPV-Proofer 7; types 16/18/31/33/45/52/58) in a real-world quality-assurance cohort at Nordland Hospital (Bodø, Norway). Among [...] Read more.

HPV DNA–positive women with ASC-US/LSIL cytology represent a heterogeneous risk group in cervical screening and require efficient triage. We evaluated a genotype-specific 7-type HPV E6/E7 mRNA assay (PreTect HPV-Proofer 7; types 16/18/31/33/45/52/58) in a real-world quality-assurance cohort at Nordland Hospital (Bodø, Norway). Among HPV-positive women with ASC-US/LSIL reflex cytology, 225 had sufficient residual liquid-based cytology material and a valid mRNA result; 175 had complete follow-up (2022–2025) and were included. Overall, 44.6% (78/175) were mRNA-positive (ASC-US 45.2%; LSIL 43.3%). For CIN2+, sensitivity was 63.4%, specificity 61.2%, PPV 33.3%, and NPV 84.5%; CIN2+ risk was 33.3% in mRNA-positive versus 15.5% in mRNA-negative women (RR 2.16, 95% CI 1.23–3.78). For CIN3+, risk was 14.1% versus 6.2%. Genotype-specific PPVs were highest for HPV33, HPV18, HPV16, and HPV31. In a referral simulation, mRNA-guided triage reduced baseline colposcopy referrals by 55% and decreased colposcopies per detected CIN2+ by ~30%, while 15 CIN2+ and 6 CIN3+ occurred in the mRNA-negative group and would be expected to be detected at 12-month follow-up among women with persistent HPV positivity. Genotype-aware HPV E6/E7 mRNA triage improves risk stratification and may increase screening efficiency. Full article

(This article belongs to the Special Issue Viral Oncology and Targeted Therapies for Virus-Associated Cancers)

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