Virulence[JOURNAL]
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200 papers
Bacterial extracellular vesicles as emerging platforms to combat multidrug-resistant bacterial infections: Mechanisms, therapeutic applications, and future prospects.
Zhou Z, Shi Y, Fu Y … +3 more , Huang Y, Song Y, Li C
Virulence · 2026 Dec · PMID 42083830 · Full text
Multidrug-resistant bacteria (MDRB) have become a global health crisis that challenges the effectiveness of conventional antibiotics. Bacterial extracellular vesicles (BEVs) are nanoscale bilayered membrane vesicles secr...
Multidrug-resistant bacteria (MDRB) have become a global health crisis that challenges the effectiveness of conventional antibiotics. Bacterial extracellular vesicles (BEVs) are nanoscale bilayered membrane vesicles secreted by both Gram-positive and Gram-negative bacteria. They can encapsulate proteins, lipids, and nucleic acids, and transfer these molecules between bacteria and host cells without direct contact. Owing to their natural ability to transport bioactive molecules, BEVs have recently gained attention as potential anti-infective platforms. They can deliver antimicrobial agents directly to resistant pathogens and act as vaccine carriers by triggering innate and adaptive immunity. Advances in BEV isolation, drug loading, and bioengineering have expanded their therapeutic potential. However, challenges such as large-scale manufacturing, immunogenicity control, and regulatory standardization still hinder clinical translation. This review summarizes the mechanisms, engineering strategies, and biomedical applications of BEVs against MDRB and discusses future perspectives for their safe and effective clinical use as antimicrobial nanoplatforms.
Genomic analyses identify nosocomial transmission of ST23 carbapenem-resistant hypervirulent mediated by a conjugative IncFII NDM-1 plasmid.
Chen T, Wang X, Xiong L … +5 more , Geng Y, Ding H, Chen Y, Shen P, Xiao Y
Virulence · 2026 Dec · PMID 42070149 · Full text
The World Health Organization has identified ST23 carbapenem-resistant hypervirulent (CR-hvKP) as a critical public health threat. Through China's national surveillance system (BRICS), we identified and characterized ST...
The World Health Organization has identified ST23 carbapenem-resistant hypervirulent (CR-hvKP) as a critical public health threat. Through China's national surveillance system (BRICS), we identified and characterized ST23 CR-hvKP bloodstream isolates from 2019-2023. Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected across two hospitals, including a nosocomial transmission pair (differing by only 2 core SNPs). Clinical outcomes revealed that three of the four patients achieved recovery following appropriate antibiotic therapy, with one mortality case attributed to underlying comorbidities. All four ST23 isolates demonstrated resistance to multiple antibiotics, indicating a pattern of multidrug resistance. Genomic analysis uncovered diverse resistance mechanisms: the nosocomial transmission pair possessed conjugative IncFII NDM-1 plasmids, while the others harbored conjugative IncFII KPC-2 plasmids, which exhibited reduced carbapenem resistance attributed to the downregulation of expression. Conjugation assays revealed high transferability (10 for IncFII NDM-1; 10 for IncFII KPC-2). Whole-plasmid comparative genomics analysis suggested that the IncFII NDM-1 plasmids shared > 99% identity with historical IncFII plasmid backbones from Chinese isolates (2014-2022), suggesting local evolution. Notably, only 4.4% (26/590) of global IncFII plasmids carried and all IncFII NDM-1 plasmids maintain conjugative potential. All strains harbored conserved virulence plasmids and maintained hypervirulence, as indicated by a mouse infection model, with the exception of one strain that exhibited mutations. This study reports the first genomic evidence of a high-frequency conjugative IncFII NDM-1 plasmid in a hospital-transmitted ST23 CR-hvKP clone, highlighting the need for plasmid-focused surveillance to control this potential threat.
Epigenetic analysis of sheep mycoplasma pneumonia and the effect of on infection.
Huang K, Cheng J, Lu Q … +7 more , Peng J, Han K, Zhang X, Yuan L, Tian H, Li F, Wang W
Virulence · 2026 Dec · PMID 42070147 · Full text
Mycoplasma pneumonia (MP), as a global infectious disease in sheep, seriously affects the production performance of sheep and economic benefits of sheep industry. However, current research on sheep resistance to MP remai...
Mycoplasma pneumonia (MP), as a global infectious disease in sheep, seriously affects the production performance of sheep and economic benefits of sheep industry. However, current research on sheep resistance to MP remains limited. To address this gap and explore the potential epigenetic regulation of sheep MP resistant, this study employed high-throughput sequencing techniques (ATAC-Seq and CUT&Tag) to analyze epigenetic modifications in lung tissue from healthy and MP-affected sheep and reveal differential epigenetic landscapes associated with disease resistance. Integrating transcriptome analysis related to MP and genome-wide association studies (GWAS), was identified as a candidate gene for MP-resistance in sheep. We established a (MO)-infected sheep alveolar epithelial cell model and regulated expression in cells through interference and overexpression techniques to study MO's adhesion and damage. The results showed that activation promoters or enhancer elements in introns of healthy lungs may enhance its transcription. overexpression reduced MO-mediated adhesion damage to cells, while knock-down increased it. Our work has enriched the gene pool for anti-pneumonia and studied the role of the gene in MO-infected cells, accumulating reliable genetic resources for sheep MP disease resistant breeding.
Conserved deletion of two consecutive glycine residues in the 100K protein is a critical determinant of FAdV-11 pathogenicity.
Wang B, Qiu L, Zhu Y … +13 more , Xiang M, Qiao Q, Yang P, Xu M, Cong Y, Zhang Y, Xu M, Qiu J, Zhang B, Yang D, Li J, Yu K, Zhao J
Virulence · 2026 Dec · PMID 42056757 · Full text
Fowl adenovirus serotype 11 (FAdV-11) causes inclusion body hepatitis, posing a persistent threat to poultry health. However, the genetic determinants governing its pathogenicity remain unclear. Comparative analysis of p...
Fowl adenovirus serotype 11 (FAdV-11) causes inclusion body hepatitis, posing a persistent threat to poultry health. However, the genetic determinants governing its pathogenicity remain unclear. Comparative analysis of pathogenic and nonpathogenic FAdV-11 strains revealed that nonpathogenic strains exhibit a conserved deletion of two consecutive glycine residues (Δ2G) in the glycine-rich domain of the 100K protein. This deletion is associated with a corresponding two-glutamic-acid deletion (Δ2E) in the glutamic acid-rich domain of the 33K protein. Here, we investigated the functional significance of two consecutive glycine residues in the virulence of FAdV-11 using the reverse genetics system of a pathogenic FAdV-11 strain. A recombinant mutant, rFAdV-11-100K-Δ2G, was generated with a seamless deletion of 2G in 100K. The replication capacity of rFAdV-11-100K-Δ2G was significantly attenuated in LMH cells, with an 8-fold reduction in peak titer versus the wild-type FAdV-11. Mechanistically, co-immunoprecipitation revealed a 1.83-fold decrease in 100K-Δ2G-Hexon binding ( < 0.001), while confocal microscopy showed impaired cytoplasmic colocalization of 100K-Δ2G and Hexon ( < 0.01). Electron microscopy results showed that the assembly of the recombinant virus rFAdV-11-100K-Δ2G was significantly inhibited in LMH cells. The concurrent Δ2E in 33K led to suppressed late gene expression. , the mutant caused only 10% mortality in SPF chickens versus 100% for the wild-type, with attenuated pathology and viral load. These results identify the two glycine residues as critical virulence determinants of FAdV-11, essential for both viral assembly and late gene regulation, thereby providing potential targets for developing attenuated vaccines.
: Mechanisms of antibiotic resistance, quorum sensing regulation, and current therapeutic strategies.
Fortaleza JAG, Cabuhat KSP, Ong CJN … +3 more , Mortel FA, Bacalzo GD, Nuevo JJM
Virulence · 2026 Dec · PMID 42056714 · Full text
has emerged as a major global pathogen due to extensive resistance to last-resort antimicrobials, a high burden of nosocomial infections, and increasing community-acquired cases. Its adaptability is driven by diverse res...
has emerged as a major global pathogen due to extensive resistance to last-resort antimicrobials, a high burden of nosocomial infections, and increasing community-acquired cases. Its adaptability is driven by diverse resistance mechanisms, including β-lactamase production, aminoglycoside-modifying enzymes, efflux pump overexpression, target-site mutations, and lipid A remodeling, all of which limit treatment options and worsen clinical outcomes. Pathogenicity is further enhanced by quorum-sensing systems, particularly AbaI/AbaR, which regulate biofilm formation, virulence, and antimicrobial tolerance. Despite extensive research, resistance, quorum sensing, and therapeutic strategies are often examined separately, limiting mechanistic understanding. This review integrates current evidence on the interplay between resistance evolution, quorum sensing, and biofilm persistence, linking these to therapeutic vulnerabilities. It further evaluates emerging interventions, including optimized antibiotic combinations, immunomodulation, drug repurposing, bacteriophage therapy, and alternative approaches, such as antimicrobial peptides, phytochemicals, nanotechnology, and photodynamic therapy to inform improved treatment strategies.
Correction.
Virulence · 2026 Dec · PMID 42054157 · Full text
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A non-structural protein 2C and 3A-specific T cell-epitopes promote inactivated vaccine efficacy in pigs via synergistic cellular and humoral immunity.
Mu S, Wang S, Dong H … +5 more , Li S, Chen L, Shang S, Guo H, Sun S
Virulence · 2026 Dec · PMID 42054148 · Full text
A (SVA) infection causes vesicular disease in swine, which presents with clinical signs that are highly similar to those of foot-and-mouth disease, and thus leads to significant challenges for disease control. Although i...
A (SVA) infection causes vesicular disease in swine, which presents with clinical signs that are highly similar to those of foot-and-mouth disease, and thus leads to significant challenges for disease control. Although inactivated SVA vaccines effectively elicit humoral immunity, they induce sub-optimal cellular immune responses. To overcome this limitation, we systematically screened T-cell epitopes within the immunogenic non-structural proteins 2C and 3A of SVA to evaluate their potential as novel immune enhancers. Forty-four overlapping peptides spanning the full-length 2C/3A proteins were synthesized. Their capacity to stimulate IFN-γ T cell responses in peripheral blood mononuclear cells from SVA-infected pigs were assessed and six immunodominant T cell epitopes (2C-5/6/7/8/14, 3A-38) were identified. Notably, epitope 2C-5 activated both CD4 and CD8 T cells and promoted their proliferation. A recombinant protein incorporating these identified T cell epitopes was designed as an immuno-stimulant and co-administered with inactivated vaccine in pigs. Challenge experiments demonstrated complete absence of clinical symptoms and undetectable viremia in the inactivated vaccine alone and co-stimulation with the inactivated vaccine and the recombinant protein groups. Notably, the combination vaccine induced significantly higher epitope-specific IFN-γ T cell responses and neutralizing antibody titers at 28 days post-vaccination compared to the inactivated vaccine alone, implying that synergistic cellular and humoral immunity may contribute to enhanced protective efficacy. This study identified promising candidate components for developing efficacious SVA vaccines, while the identified conserved T cell epitopes provided a critical foundation for designing broad-spectrum multi-epitope vaccines.
Micafungin microevolution in reveals resistance development without fitness compromise.
Bohner F, Szilovics Z, Veres É … +3 more , Papp C, Nosanchuk JD, Gácser A
Virulence · 2026 Dec · PMID 42051239 · Full text
is an emerging multidrug-resistant pathogen with high transmissibility in healthcare settings. Although echinocandin resistance in is typically associated with fitness loss, we found that micafungin-resistant strains (...
is an emerging multidrug-resistant pathogen with high transmissibility in healthcare settings. Although echinocandin resistance in is typically associated with fitness loss, we found that micafungin-resistant strains (MICA) generated from two distinct source isolates (AR0381 and AR0387) via experimental microevolution retained full virulence. Evolved strains developed stable resistance to multiple echinocandins, while AR0387 (B8441), originating from MICA strain, also acquired increased azole tolerance. Whole-genome sequencing revealed clinically relevant mutations in , as well as changes in genes involved in ergosterol biosynthesis (), amino acid metabolism, and PKA signaling. Despite sensitivity to cell wall stressors, resistant strains maintained or even enhanced colonization in a murine systemic infection model. Independently evolved strains showed similar antifungal resistance profiles, and although minor differences of pathogenic potential were noted, no consistent virulence attenuation was observed, indicating the reproducibility of phenotype changes. These findings suggest that can acquire echinocandin resistance without compromising pathogenicity, supporting its persistence and spread in clinical settings.
Synergistic antibacterial activity and mechanism of arginine combined with florfenicol against .
Cao M, Li Y, Han G … +7 more , Liu H, Xiong S, Liu X, Zhao M, Su Y, Li Y, Dong C
Virulence · 2026 Dec · PMID 42047263 · Full text
The persistent escalation of antibiotic resistance poses a severe threat to global public health. As a common opportunistic pathogen, the rapid development of resistance in () poses severe challenges to clinical anti-in...
The persistent escalation of antibiotic resistance poses a severe threat to global public health. As a common opportunistic pathogen, the rapid development of resistance in () poses severe challenges to clinical anti-infective therapy. Against this backdrop, the combined use of amino acids and antibiotics is considered an effective strategy against multidrug-resistant bacterial infections. This study investigated the antibacterial efficacy and mechanism of action of the combination of arginine (Arg) and florfenicol (FFC) against resistant . Results indicate that Arg significantly enhances the bactericidal activity of FFC against resistant both and , successfully reversing the resistance phenotype. Mechanistic studies reveal that Arg disrupts fatty acid β-oxidation by inhibiting the arginine succinyl-transferase (AST) pathway, leading to excessive free fatty acid (FFA) accumulation. This triggers membrane structural damage, energy metabolism disorders, and oxidative stress. Concurrently, Arg inhibits the expression and function of multidrug efflux pumps, such as AcrAB-TolC and EmrAB-TolC, reducing FFC efflux and increasing its intracellular concentration. This study systematically reveals a novel pathway whereby Arg synergistically enhances the antibacterial activity of FFC through dual mechanisms of metabolic reprogramming and efflux pump inhibition, providing theoretical support for the development and application of amino acid compounds as antibiotic adjuvants.
Characterization of the intrahepatic microbiome in patients with HBV-related end-stage liver disease.
Chen J, Liang T, Xu X … +25 more , Yu X, Li Z, Zheng X, Liu Y, Yang S, Meng Z, Zhou Y, Ye C, Tu H, Cao G, Chen H, Chen L, Li B, Nie Y, Sun S, Zhang Y, Lu Y, Zhang X, Yu G, Lv Y, Jia H, Deng Z, Pei N, Shi Y, Yang Y
Virulence · 2026 Dec · PMID 42041114 · Full text
BACKGROUND: Dysregulated microbiota is a hallmark of end-stage liver disease (ESLD). This study aimed to elucidate the intrahepatic microbiome in hepatitis B virus (HBV)-related ESLD. METHODS: We collected liver tissue s...
BACKGROUND: Dysregulated microbiota is a hallmark of end-stage liver disease (ESLD). This study aimed to elucidate the intrahepatic microbiome in hepatitis B virus (HBV)-related ESLD. METHODS: We collected liver tissue samples from patients undergoing liver transplantation due to decompensated cirrhosis (DC) ( = 20) or acute-on-chronic liver failure (ACLF) ( = 24), as well as 18 samples from donors. Metatranscriptomic sequencing was performed to profile liver microbiome and transcriptome. RESULTS: 2208 bacterial species were detected across 13 phyla and 165 genera. Metatranscriptomic profiling revealed that and dominated the intrahepatic microbiome, with and most prevalent across groups. Principal coordinate analysis showed distinct microbial community structures among donors, DC, and ACLF patients. Compared with donors, both groups exhibited increased abundance of , , and , while ACLF patients were further enriched with and , and DC patients had higher . Most taxa originated from the gut, with additional oral- and respiratory-derived species. Despite similar abundance between groups, in ESLD displayed marked functional activation, including nutrient acquisition systems and virulence factors linked to adhesion, invasion, and toxin production. Integrated host - microbiome analysis revealed taxa-specific associations with impaired hepatic metabolic, immune, and structural integrity. CONCLUSION: This study delineates the compositional and functional reprogramming of the intrahepatic microbiome in patients with ESLD and its coupling with liver metabolic, immune, and structural pathways. These findings suggest the intrahepatic microbiome as a promising therapeutic target for ESLD.
Novel Taiwan-I-type infectious bronchitis virus: First evidence of testicular atrophy and efficacious protection with strain-matched oil-emulsified inactivated vaccine.
Zhang T, Xie Y, Yang C … +15 more , Guan M, Lu C, Lin Z, Li J, Dai J, Zhang C, Yang R, Wu Q, Wang Q, Li Y, Wu Q, Wei T, Huang J, Huang T, Mo M
Virulence · 2026 Dec · PMID 42035485 · Full text
The Taiwan-I-type infectious bronchitis virus (IBV) has become one of the most dominant and threatening genotypes circulating in China poultry farms. In this study, we characterized the Taiwan-I-type IBV strain GX-NN2007...
The Taiwan-I-type infectious bronchitis virus (IBV) has become one of the most dominant and threatening genotypes circulating in China poultry farms. In this study, we characterized the Taiwan-I-type IBV strain GX-NN200723 and evaluated its pathogenicity and vaccine potential. Phylogenetic and recombination analyses revealed that the strain shared the highest nucleotide similarity with the vaccine strain QXL87 and originated from a recombination event between CK/CH/LSC-99I (major parent) and TW2575/98 (I) (minor parent) within the S1 gene region. Notably, epitope mapping showed significant differences in the number and sequence of antigenic sites compared to commonly used vaccine strains (H120, 4/91, QXL87, LDT3-A), and these differences may largely account for the poor cross-protection and frequent vaccine failures observed in the field. Pathogenicity assessment in 7-day-old SPF chicks demonstrated broad tissue tropism of the strain, causing 30% mortality along with severe reproductive disorders, notably, testicular atrophy in males was observed for the first time in Taiwan-I-type IBV. Furthermore, an oil-emulsified inactivated vaccine (OEIV) developed from the GX-NN200723 strain induced strong humoral and cell-dependent immune responses. Protective efficacy was only evaluated against homologous challenge in this study, the GX-NN200723-OEIV group exhibited 100% survival, the mildest clinical signs, minimal pathological damage, and the lowest viral shedding among all immunized groups. These findings support the use of the GX-NN200723-OEIV as a promising candidate vaccine for controlling Taiwan-I-type IBV infection. This study provides critical insights into the evolution, pathogenesis, and immunization strategies against this economically significant poultry pathogen.
Pathogenicity and virulence of .
Sundin GW, Castiblanco LF, Zeng Q
Virulence · 2026 Dec · PMID 42035484 · Full text
Fire blight, caused by the bacterial pathogen , is the most significant global threat to commercial apple and pear production. Outbreaks resulting in flower infection cause yield losses accompanied by internal systemic s...
Fire blight, caused by the bacterial pathogen , is the most significant global threat to commercial apple and pear production. Outbreaks resulting in flower infection cause yield losses accompanied by internal systemic spread of pathogen cells through trees that can lead to tree death in a single season. The type III secretion system and the exopolysaccharide (EPS) amylovoran are pathogenicity factors, and biofilm formation in leaf xylem is a critical virulence factor. We review our current knowledge of pathogenesis and how pathogenesis strategies intersect and facilitate systemic movement in the host. Fire blight management remains extremely difficult due to the high susceptibility of host plants and the aggressive virulence of the pathogen. We suggest that future management will rely on innovative strategies for resistance breeding or those that directly target bacterial populations and condition the host by eliciting a resistance response prior to pathogen arrival.
Emerging threat of Oropouche virus: Clinical features, experimental models, and virulence.
Alkan C, Ikegami T
Virulence · 2026 Dec · PMID 42035480 · Full text
Oropouche fever, caused by Oropouche virus (OROV) and transmitted primarily by midges, has historically been considered a neglected tropical disease characterized by an acute, self-limiting febrile illness and occasiona...
Oropouche fever, caused by Oropouche virus (OROV) and transmitted primarily by midges, has historically been considered a neglected tropical disease characterized by an acute, self-limiting febrile illness and occasional meningoencephalitis, mostly within or along the Amazon rainforest. However, the explosive 2023-2025 outbreak expanded well beyond the Amazon region, including into the Caribbean, and was associated with a broader clinical spectrum encompassing meningoencephalitis, Guillain - Barré syndrome, persistent viral infection, lethal hemorrhagic fever, fetal loss, and neonatal abnormalities. Experimental animal models of OROV infection are available; however, substantial variation in host susceptibility across species complicates the interpretation of pathogenic mechanisms. The major virulence factor, the NSs protein, mediates inhibition of host cellular transcription, whereas the biological functions of the NSm protein remain largely unknown. This review outlines current knowledge on OROV outbreaks, clinical features, animal models, and virulence determinants, underscoring major knowledge gaps in understanding OROV virulence and pathogenesis.
Linking oxidative stress defense to biofilm architecture: Ohr mediates strain-dependent persistence in .
Yu R, Al-Shamiri MM, Zhang S … +9 more , Li P, Lei C, Liu H, Xue L, Luo K, Han B, Xun M, Yang E, Han L
Virulence · 2026 Dec · PMID 42035474 · Full text
Biofilm formation is critical for the persistence of , yet its directional correlation with antimicrobial resistance remains paradoxical. Here, we confirmed our prior finding that drug-sensitive and multidrug-resistant (...
Biofilm formation is critical for the persistence of , yet its directional correlation with antimicrobial resistance remains paradoxical. Here, we confirmed our prior finding that drug-sensitive and multidrug-resistant (MDR) strains employ distinct, temporally regulated biofilm developmental programs: susceptible strains excel at rapid biomass accumulation but undergo early collapse, while MDR strains delay biofilm initiation and optimize for the maintenance and reinforcement of mature biofilms. Transcriptomic profiling identified the organic hydroperoxide resistance protein (Ohr) as a crucial contributor mediating this strain-specific biofilm divergence, with its deletion resulting in severe biofilm defects. Metabolomics analyses further revealed that Ohr maintains biofilm integrity through dual mechanisms: by modulating redox homeostasis and regulating extracellular polymeric substance (EPS) production through control of AdeAB and AdeFG efflux pumps. Moreover, we identified indole-3-lactic acid as a potent biofilm inhibitor. Our findings suggest Ohr as a linchpin in biofilm development, elucidate the basis of temporal phenotypic divergence, and unveil promising therapeutic targets against biofilm-associated infections.
3C suppresses PINK1-mediated mitophagy and contributes to coxsackievirus B3 replication.
Liu T, Wan A, Xu Y … +10 more , Lu H, Xie Y, Wu H, Wang J, Wang H, Hao T, Zhang Y, Xu J, Shen H, Li S
Virulence · 2026 Dec · PMID 42035472 · Full text
Viral myocarditis (VM) is a cardiac inflammatory condition caused by viral infection and serves as a critical precursor to life-threatening complications, such as dilated cardiomyopathy and heart failure. Coxsackievirus...
Viral myocarditis (VM) is a cardiac inflammatory condition caused by viral infection and serves as a critical precursor to life-threatening complications, such as dilated cardiomyopathy and heart failure. Coxsackievirus B3 (CVB3), a predominant etiological agent of VM, lacks targeted therapeutic interventions despite ongoing antiviral development. Mitophagy is a selective mitochondrial quality control mechanism mediated by PINK1. It has two key roles: maintaining mitochondrial homeostasis and regulating innate antiviral immunity. Here, we employed single-cell RNA sequencing to reveal a significant correlation between impaired mitophagy and cardiomyocyte pathology in CVB3-induced myocarditis. We demonstrated that CVB3 infection suppresses PINK1-dependent mitophagy, while the attenuation of PINK1 reciprocally enhances CVB3 replication. Mechanistically, CVB3 non-structural protein 3C promotes the degradation of mitochondrial antiviral signaling protein (MAVS). MAVS interacts with PINK1 to form a regulatory loop: PINK1 deficiency boosts MAVS reduction, which further promotes viral replication and worsens myocardial injury. Furthermore, we identify the transcription factor FOSL1 as a novel negative regulator of PINK1 transcription through direct promoter binding. Collectively, these findings show that the 3C/FOSL1/PINK1/MAVS signaling axis is a key mechanism in CVB3 pathogenesis. We propose innovative therapeutic targets for viral myocarditis through restoration of mitochondrial homeostasis and modulation of host-virus interactions.
The cell-type-specific roles of Toll-like receptors in herpes simplex virus infection and pathogenesis.
Yu H, Wang L, Gong J … +3 more , Lu H, Liu W, Ding L
Virulence · 2026 Dec · PMID 42030207 · Full text
Herpes simplex virus (HSV) initiates infection in mucosal epithelial cells, forming characteristic lesions before establishing lifelong latency in sensory neurons. The innate immune response to HSV is critically mediated...
Herpes simplex virus (HSV) initiates infection in mucosal epithelial cells, forming characteristic lesions before establishing lifelong latency in sensory neurons. The innate immune response to HSV is critically mediated by the Toll-like receptor (TLR) family. Expressed in a cell‑type‑specific manner, TLRs recognize viral components, leading to the production of interferons and pro-inflammatory cytokines. Different cell populations, by virtue of their unique TLR expression profiles and signaling contexts, mount specialized and non-redundant responses to the same viral pathogen. We systematically synthesize current research to elucidate the roles of specific TLRs in major cellular targets of HSV, including mucosal epithelial cells, fibroblasts, plasmacytoid dendritic cells, macrophages, peripheral neurons, and resident central nervous system cells. By examining how TLR-mediated sensing and signaling diverge across this cellular landscape, this article provides an integrated framework for understanding the coordinated, multi-layered immune defense against HSV and highlights the implications for pathogenesis and therapeutic strategies.
Cordycepin suppresses growth and virulence of via mitochondrial function and carbonic anhydrase-associated nitrogen metabolism.
Dang Y, Li Y, Xu G … +7 more , Wang T, An Q, Gao F, Liang X, Ji X, Li Q, Wang L
Virulence · 2026 Dec · PMID 42018452 · Full text
Cordycepin, a nucleoside analog naturally produced by fungi, exhibits broad-spectrum biological activity and has been reported to inhibit both prokaryotic and eukaryotic microorganisms, although its antifungal mechanism...
Cordycepin, a nucleoside analog naturally produced by fungi, exhibits broad-spectrum biological activity and has been reported to inhibit both prokaryotic and eukaryotic microorganisms, although its antifungal mechanisms remain poorly understood. In this study, we systematically evaluated the inhibitory effects of cordycepin on the growth, development, and pathogenicity of , the causal agent of rice blast, and further elucidated its mode of action through transcriptomic analysis and gene function validation. Cordycepin significantly inhibited hyphal growth and reduced both conidial production and germination in a dose-dependent manner. Moreover, it severely impaired appressorium formation and increased the frequency of malformed structures, ultimately leading to attenuated virulence. Transcriptome profiling revealed that cordycepin reprogrammed multiple metabolic and signaling pathways, including nitrogen metabolism, fatty acid metabolism, melanin and chitin biosynthesis, and protein kinase networks. Notably, two carbonic anhydrase genes, and , were significantly downregulated and identified as candidate genes responsive to cordycepin. Functional analysis showed that MoCA5 localizes to mitochondria and interacts with MoCA1; deletion of either gene resulted in disrupted mitochondrial membrane potential, reduced ATP synthesis, and decreased pathogenicity. Collectively, our results indicate that cordycepin suppresses the growth and virulence of through coordinated modulation of mitochondrial function and nitrogen metabolism - associated pathways. These findings provide new insights into the antifungal action of cordycepin and identify potential molecular components involved in fungal metabolic adaptation to cordycepin stress.
Esculetin exhibits antifungal effects against by inhibiting titan cell formation.
Wu X, Ni Q, Chen J … +5 more , Huang X, Zheng P, Wu D, Zhang S, Lu Z
Virulence · 2026 Dec · PMID 42015479 · Full text
is responsible for pulmonary cryptococcosis and life-threatening cryptococcal meningitis, particularly in immunocompromised individuals. Despite its high mortality rate and the diagnostic challenges, current antifungal t...
is responsible for pulmonary cryptococcosis and life-threatening cryptococcal meningitis, particularly in immunocompromised individuals. Despite its high mortality rate and the diagnostic challenges, current antifungal therapies are hampered by limitations such as side effects and the emergence of drug resistance. A critical virulence factor of is its ability to form titan cells, enlarged polyploid cells that promote immune evasion and dissemination. However, therapeutic interventions specifically targeting titan cell formation remain unexplored. In this study, we investigated the antifungal activity of esculetin (6,7-dihydroxycoumarin), a natural coumarin derivative with a broad range of biological activities, against . While esculetin exhibited modest activity (MIC = 30 μg/mL) and demonstrated synergistic effects with amphotericin B against , it significantly inhibited intracellular proliferation within macrophages and reduced fungal burden in murine lungs. Esculetin treatment reduced the proportion of titan cells in the infected lungs. Subsequent investigations revealed that esculetin directly inhibits titan cell formation . Limited proteolysis-mass spectrometry (Lip-MS) and molecular docking analyses identified CNAG_03983, an oxidoreductase involved in carbohydrate metabolism, as a potential molecular target of esculetin. Quantitative PCR analysis showed that esculetin treatment altered the expression of key components of the cAMP/PKA signaling pathway, including , , , , , and , suggesting that esculetin may inhibit titan cell formation by perturbing cAMP/PKA signaling. These findings highlight the potential of esculetin as a novel antifungal strategy against , primarily through its capacity to disrupt titan cell formation and modulate associated signaling pathways.
Impact of antiviral treatment and initiation time on mother-to-child transmission in pregnant women with extremely high HBV DNA loads.
Yi W, Cao W, Wan G … +6 more , Wang S, Deng W, Zhang Z, Li X, Xie Y, Li M
Virulence · 2026 Dec · PMID 42003011 · Full text
To further reduce mother-to-child transmission (MTCT), this study aims to explore the factors influencing MTCT rate in pregnant women with extremely high HBV DNA loads (HBV DNA ≥ 1 × 10 IU/ml). In this retrospective real...
To further reduce mother-to-child transmission (MTCT), this study aims to explore the factors influencing MTCT rate in pregnant women with extremely high HBV DNA loads (HBV DNA ≥ 1 × 10 IU/ml). In this retrospective real-world study, pregnant women with chronic hepatitis B virus (HBV) infection and their infants were analyzed. Pregnant women received antiviral therapy during the second or third trimester based on their HBV DNA loads and personal preferences. Newborns were administered hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine within 6 h after birth, while their HBV infection status was followed up after 7 months. Data from 4,157 pregnant women and 4192 infants were collected. All 35 cases of MTCT occurred in mothers with extremely high HBV DNA loads (1570 mothers and 1588 infants), of which 29 cases were in nonantiviral therapy group, and 6 in antiviral therapy group. Antiviral treatment could markedly reduce MTCT rate ( < 0.001). The decrease of HBV DNA loads below 1 × 10 IU/ml or above didn't impact MTCT rate after antiviral treatment. The average initiating antiviral treatment time among mothers with MTCT was significantly later than mothers without MTCT ( = 0.008). In the absence of antiviral treatment, predelivery HBV DNA levels in mothers with MTCT were higher compared to those without MTCT ( = 0.001). MTCT mainly occurred in pregnant women with extremely high HBV DNA loads; however, antiviral treatment could reduce MTCT rate. The efficacy of antiviral drugs did not affect the incidence of MTCT, but early initiation of antiviral treatment may contribute to a decrease in its occurrence.
Synergetic attenuated inflammatory response and increased apoptosis confer high pathogenicity of .
Liu L, Yang L, Xie Q … +5 more , Qi X, Pan H, Dong HP, Zheng X, Xu T
Virulence · 2026 Dec · PMID 41995040 · Full text
has emerged as a major global healthcare threat, ranking among the leading causes of both hospital-acquired and community-acquired infections. Its extensive antibiotic resistance complicates treatment, underscoring the n...
has emerged as a major global healthcare threat, ranking among the leading causes of both hospital-acquired and community-acquired infections. Its extensive antibiotic resistance complicates treatment, underscoring the need for therapeutic targets that elicit robust immune responses. This study identified two multidrug-resistant clinical strains of (rough) and (smooth). has thick and dense capsular polysaccharide, and exhibits high pathogenicity by suppressing host inflammatory responses and inducing apoptosis to evade immune surveillance. Conversely, possesses a thin capsular polysaccharide and triggers pyroptosis via inflammasome activation, causing pronounced inflammation. RNA-sequencing revealed that capsule polysaccharide, transmembrane secretion systems, and nutrient acquisition systems of might contribute to the induction of apoptosis. Our study reveals different roles of apoptosis and pyroptosis in the pathogenicity of and provides potential therapeutic targets against infections.
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