Virulence[JOURNAL]
Sun
200 papers
Unveiling the conserved mechanism of microsporidian vertical transmission: A comparative study of infection across host species.
Wang C, Kong Y, Tang Z … +5 more , Luo T, Yang X, Zhang Y, Li T, Zhou Z
Virulence · 2026 Dec · PMID 41437514 · Full text
Microsporidia, ubiquitous obligate intracellular parasites infecting a wide range of hosts from humans to economically vital animals, employ transovarial transmission (TOT) as their primary vertical transmission mode. De...
Microsporidia, ubiquitous obligate intracellular parasites infecting a wide range of hosts from humans to economically vital animals, employ transovarial transmission (TOT) as their primary vertical transmission mode. Despite its significance, the mechanisms underpinning microsporidian TOT have remained elusive. This study comparatively analyzed the TOT in two distinct systems: infecting wild tussah , and infecting domestic silkworms and crop pests and . Our findings reveal that both parasites share a conserved invasion sequence targeting ovariole sheath cells, follicular cells, nurse cells, and ultimately oocytes. Notably, infection of follicular and nurse cells consistently precedes oocyte invasion, suggesting a strategic utilization of these cells for efficient transmission. Contrasting patterns were observed between the two parasites: while exhibits lower infection rates and produces mature spores in both oocytes and nurse cells, displays higher parasite loads with proliferative stages predominant throughout infection. A critical innovation emerges from our RNA interference experiments, where knockdown of host vitellogenin (Vg) significantly reduced microsporidian loads, identifying Vg as a conserved molecular facilitator in TOT. These findings not only elucidate the evolutionary conservation of vertical transmission mechanisms among microsporidia but also pinpoint Vg as a promising target for intervention against these pathogens. This research advances our understanding of vertical transmission of fungal parasites and offers novel avenues for disease control.
Otilonium bromide exhibits novel antifungal activity against via regulating iron homeostasis.
Hsu LH, Chou YP, Shen TL … +2 more , Wieczorek D, Chen YL
Virulence · 2026 Dec · PMID 41437513 · Full text
Traditional antifungal drugs used against have several drawbacks, including the emergence of drug-resistant strains. In addition, developing novel antifungal agents requires long-term research and design. Drug repurposi...
Traditional antifungal drugs used against have several drawbacks, including the emergence of drug-resistant strains. In addition, developing novel antifungal agents requires long-term research and design. Drug repurposing, identifying and utilizing previously unknown functions of known drugs, such as antifungal activity, may be a quick method for mining efficient alternatives. Otilonium bromide (OB), an FDA-approved drug, is a quaternary ammonium compound used as a therapeutic drug for irritable bowel syndrome. We previously reported the inhibitory effect of OB against the spore germination of . In this study, we found that the antifungal activity of OB against was 2 μg/mL for both minimum inhibitory and fungicidal concentrations. OB could destroy the cell membrane and prevent from undergoing yeast-to-hyphae transition, thus interfering with biofilm formation. Additionally, the efficacy of OB was abolished when iron ions were provided, suggesting that iron homeostasis was associated with the inhibition mechanism of OB. Interestingly, a therapeutic assay showed that OB demonstrated limited efficacy in reducing burden in a murine systemic infection model. In summary, repurposing OB against may facilitate the design of new antifungal drugs, and chemical modification could enhance the efficacy of OB to be more specific to fungal pathogens.
Protocatechuic acid attenuated inflammation caused by and its metabolites.
Gong J, Ma S, Xiang H … +7 more , Yang X, Zhang W, Hu R, Liu M, Fan Z, He J, Wu S
Virulence · 2026 Dec · PMID 41437510 · Full text
Gut microbiota has been considered as a key bridge between phytochemicals and host immunity. ( showed a close correlation with inflammation, and protocatechuic acid (PCA) has potential protective effects in our previous...
Gut microbiota has been considered as a key bridge between phytochemicals and host immunity. ( showed a close correlation with inflammation, and protocatechuic acid (PCA) has potential protective effects in our previous studies. To understand the underlying mechanism, a total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly assigned into 3 groups, with 6 replicates and 6 piglets per replicate. The piglets were fed a basal diet, a basal diet containing 1.0 × 10 CFU/kg or 1.0 × 10 CFU/kg +400 mg/kg PCA for 28 d. Results showed that decreased the final body weight and average daily gain (ADG), while increased the feed-to-gain ratio (F/G), with increased serum levels of interleukin (IL)-2 and IL-8 in piglets (), and reduced the expression of intestinal tight junction protein (). Dietary supplementation of PCA increased the ADG by suppressing inflammation and enhancing intestinal integrity. In vitro experiments demonstrated that argininosuccinic acid, indole-3-aldehyde, and N-acetylputrescine are critical metabolites produced by , which initiated inflammatory responses by upregulating pro-inflammatory cytokines and downregulating tight junction proteins in MODE-K cells. PCA was found to effectively attenuate these effects in a dose-dependent manner. In conclusion, PCA can improve the growth performance in weaned piglets by attenuating inflammation caused by and its metabolites.
Differential roles of HSP70 and HSP90 in Senecavirus A infection: IRES-dependent translational regulation and viral replication mechanisms.
Li C, Ma Y, Liu C … +3 more , Xu S, Shi J, Li J
Virulence · 2026 Dec · PMID 41412139 · Full text
As opportunistic intracellular pathogens, viruses rely on numerous sequential interactions between host and viral factors for their replication. Given the significance of molecular chaperones (heat shock protein 70 and h...
As opportunistic intracellular pathogens, viruses rely on numerous sequential interactions between host and viral factors for their replication. Given the significance of molecular chaperones (heat shock protein 70 and heat shock protein 90) in mediating protein homeostasis, research has suggested that they are involved in viral infections in many ways. This study explored the roles of HSP70 and HSP90 in the Senecavirus A (SVA) life cycle. We demonstrate that HSP70 and HSP90 regulate virus internal ribosome entry site (IRES)-dependent translation activity by acting on SVA IRES. Additionally, we show that HSP70 promotes SVA IRES-dependent translation through association with SVA IRES domain II, and HSP90 may function through interaction with SVA IRES domain IV. Furthermore, we found that the structural proteins and four non-structural proteins (Lpro, 2B, 2C, 3A) were shown to interact with HSP70 and HSP90. Furthermore, we determined that HSP70 and Hsp90 activity is important for virus replication by stabilizing SVA proteins and preventing their degradation via the ubiquitin-proteasome, apoptosis, and autophagy-lysosome pathway. Our findings indicate that HSP70 and HSP90 activity is essential for SVA replication, offering new insights into the development of potential specific control strategies against SVA infection.
The autophagy-related protein PlAtg26b regulates vegetative growth, reproductive processes, autophagy, and pathogenicity in .
Wang X, Yu G, Luo Y … +5 more , Chen T, Zhang X, Ye L, Yang C, Chen Q
Virulence · 2026 Dec · PMID 41410478 · Full text
is an oomycete pathogen responsible for litchi downy blight, a significant threat to global litchi production. Autophagy, a conserved degradation pathway crucial for the growth, development, and pathogenicity of phytopat...
is an oomycete pathogen responsible for litchi downy blight, a significant threat to global litchi production. Autophagy, a conserved degradation pathway crucial for the growth, development, and pathogenicity of phytopathogenic organisms, remains an area of active investigation. In this study, we characterized the function of the Atg26 homolog PlAtg26b in . Using the CRISPR/Cas9 genome editing system, we generated knockout mutants and determined that PlAtg26b localizes to mitochondria under stress conditions. Although deletion of did not impair selective autophagy, it markedly reduced Atg8-PE synthesis, vegetative hyphal growth, asexual and sexual reproduction, and zoospore release. Furthermore, -deficient mutants exhibited significantly reduced virulence on litchi fruits and leaves. Collectively, our findings demonstrate that PlAtg26b plays a pivotal role in the biological development and pathogenicity of .
Small regulatory RNAs mediated regulation of virulence and host-pathogen interaction in the Gram-negative ESKAPE pathogens.
Li L, Zhang Z, Zhu H … +10 more , Cui K, Song X, Wang Z, Chen L, Yu Z, Zhang W, Sun H, Yu Z, Duan Y, Li M
Virulence · 2026 Dec · PMID 41410397 · Full text
The emergence and global spread of antimicrobial resistant (AMR) pathogens represent a critical challenge to global public health security. The ESKAPE pathogens refer to a group of highly troublesome multidrug-resistant...
The emergence and global spread of antimicrobial resistant (AMR) pathogens represent a critical challenge to global public health security. The ESKAPE pathogens refer to a group of highly troublesome multidrug-resistant bacteria responsible for hospital-acquired infections. Of particular concern are Gram-negative ESKAPE pathogens, which pose a significant threat to patient health and healthcare systems worldwide. Systematic investigation into antimicrobial resistance mechanisms and pathogenicity regulation is therefore imperative for developing effective infection control strategies. Emerging evidence highlights small regulatory RNAs (sRNAs) as pivotal post-transcriptional modulators in bacterial physiology, particularly in governing virulence determinant expression and host-pathogen interactions during infection. This review summarizes recent advances in sRNA-mediated regulatory mechanisms in Gram-negative ESKAPE pathogens, with emphasis on , , and . We discuss the classification of sRNAs, their regulatory mechanisms, their roles in modulating virulence factors and pathogenicity, as well as the challenges and opportunities in targeting sRNAs for antimicrobial therapy. Evidence accumulated across the studies reviewed indicates that sRNAs exert their function through base pairing with target mRNAs or other sRNA, through interactions with proteins, or as dual-function sRNA. sRNAs have emerged as essential regulators of virulence in the ESKAPE pathogens, influencing capsular polysaccharide production, iron acquisition, biofilm formation, regulation of catabolic pathway genes, cell adhesion and invasion, as well as host immune responses during infection. This review provides a framework for understanding bacterial adaptive evolution through sRNA-mediated regulation and identifies novel intervention targets against multidrug-resistant pathogens.
A mycovirus shaped insect-pathogenic and non-pathogenic phenotypes in a fungal biocontrol agent.
Rueda-Maíllo F, García Del Rosal MJ, Garrido-Jurado I … +1 more , Quesada-Moraga E
Virulence · 2026 Dec · PMID 41408592 · Full text
Mycoviruses are increasingly recognized for their potential applications in crop protection, particularly in biocontrol of phytopathogenic fungi and in enhancement of the environmental competence and virulence of entomop...
Mycoviruses are increasingly recognized for their potential applications in crop protection, particularly in biocontrol of phytopathogenic fungi and in enhancement of the environmental competence and virulence of entomopathogenic ascomycetes (EA) to optimize their pest control potential. Here, we provide the first evidence of a functional switch between insect-pathogenic and nonpathogenic states in a strain of the EA , driven by a victorivirus 1 (BbVV-1) acting as an essential virulence determinant. The mycovirus-infected wild-type strain (WMI) demonstrated broad-spectrum virulence across insect orders, whereas the isogenic mycovirus-free strain (MFr) was entirely nonpathogenic, exhibiting a complete suppression of cuticle penetration capability, which was restored only through injection of conidia into the hemocoel, bypassing the cuticle barrier. A comprehensive analysis of mycovirus-related inhibition of cuticle penetration revealed that WMI exhibited strong activity in extracellular cuticle-degrading enzymes (ECEs) relevant to virulence, with emphasis on Pr1 protease, whereas ECE secretion, and notably Pr1, were markedly suppressed in MFr. Insect infection by WMI showed a time-dependent increase in the number of gene copies and quantity of fungal DNA, while neither expression nor fungal DNA were detected in MFr during the infection cycle. Downregulation of the gene in MFr suggests a direct effect of mycovirus on fungal transcriptional regulation, highlighting the potential to deploy this BbVV-1 to produce hypervirulent EA strains but also to transition EA from entomopathogens to solely plant-beneficial microorganisms.
toxins mediate endothelial Thrombomodulin release during severe invasive infections.
Seidner L, Tanaka E, Engstrand O … +7 more , Nilsson S, Bergonzini A, Kaland L, Novello M, Svensson M, Norrby-Teglund A, Palma Medina LM
Virulence · 2026 Dec · PMID 41408425 · Full text
Thrombomodulin (TM) is a membrane protein with significant roles in coagulation hemostasis and immune response. Its soluble form (sTM) has recently emerged as a key biomarker for severe invasive bacterial infections, inc...
Thrombomodulin (TM) is a membrane protein with significant roles in coagulation hemostasis and immune response. Its soluble form (sTM) has recently emerged as a key biomarker for severe invasive bacterial infections, including Necrotizing Soft Tissue Infections (NSTI). While various mechanical, chemical, and enzymatic mechanisms have been linked to TM shedding, this study investigates the direct impact of bacterial stimuli on soft tissue cells as primary sources of TM release. We stimulated organotypic models, composed of fibroblast and endothelial cells, with NSTI clinical isolates and found that while Group A Streptococcus and had minimal effect on TM release, infection triggered a significant increase of sTM levels. We further assessed whether the secreted proteins of led to higher TM levels by increased expression, increased cell toxicity, or direct cleavage of TM from the endothelial cell membrane. To investigate these mechanisms, we performed stimulations of endothelial monolayers with secreted proteins of two isolates differing in their -system functionality. Our results indicate that -regulated proteins induce TM shedding by direct cleavage from the cell membrane, an effect that was inhibited by metalloproteinase inhibitors. Stimulation with the pore-forming protein α-toxin showed similar results, suggesting a potential involvement of ADAM10 in TM cleavage. Additionally, we observed that other -regulated proteins can cleave TM directly. Altogether, this study reveals a pathogen-specific mechanism for TM release during invasive infection, contributing to its elevated plasma levels and providing deeper insights into the pathophysiology of NSTI.
The gene is a fitness determinant of anaerobic growth and its inactivation affects virulence and rugose small colony variants emergence.
Baldelli V, Carrasco Aliaga SJ, Colque CA … +8 more , Mazzola F, Ravishankar S, Johansen HK, Molin S, Raffaelli N, Paroni M, Landini P, Rossi E
Virulence · 2026 Dec · PMID 41408422 · Full text
is the leading cause of death in cystic fibrosis (CF) patients, yet the genetic mechanisms driving its fitness in the host remain poorly defined. Previously collected transcriptomic data of clinical samples showed that e...
is the leading cause of death in cystic fibrosis (CF) patients, yet the genetic mechanisms driving its fitness in the host remain poorly defined. Previously collected transcriptomic data of clinical samples showed that expression of the gene PA14_RS04555 () is stimulated in the CF lung environment. In this work, we show that is regulated by the global transcriptional regulators Vfr and AmrZ. Loss of markedly enhanced pathogenicity, increasing virulence in , and promoting bacterial translocation and biofilm formation in a differentiated airway epithelial infection model. Deletion of triggered the emergence of biofilm-proficient rugose small colony variants (RSCVs), driven by elevated c-di-GMP and increased Pel polysaccharide production when cultures were grown in static conditions. The RSCV phenotype depends on suppressor mutations in the operon, possibly as a response to redox imbalance caused by the lack of under oxygen-limited conditions. Indeed, the mutant exhibited impaired fitness during anaerobic respiration when nitrate was the sole electron acceptor, in a manner independent of the ubiquinone pool. Our findings show that inactivation promotes RSCV emergence and identify as a novel genetic determinant of metabolic fitness under host-relevant conditions, thereby underscoring the role of redox balance in chronic CF infections.
Molecular characterization and pathogenicity of a novel Chinese porcine deltacoronavirus strain CH/HLJ/20 isolated from diarrheic piglets.
Wang Y, Ma X, Zhang H … +7 more , Xue X, Li J, Jiang Y, Cui W, Liu D, Zhou B, Wang L
Virulence · 2026 Dec · PMID 41408166 · Full text
Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes acute diarrhea and high mortality in neonatal piglets. In this study, we isolated and characterized a novel PDCoV strain, CH/HLJ/20, from di...
Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes acute diarrhea and high mortality in neonatal piglets. In this study, we isolated and characterized a novel PDCoV strain, CH/HLJ/20, from diarrheic piglets in Northeast China. Full-length genome sequencing and phylogenetic analysis revealed that CH/HLJ/20 belongs to the Chinese lineage but harbors distinct recombination signals within the S gene, with Korea/DH1/2017 and CHN/Tianjin/2016 identified as putative parental strains. Comparative analysis identified two unique amino acid substitutions (Q10H and N98K) within the receptor-binding domain (RBD) of the spike protein. Structural modeling and molecular docking revealed that the CH/HLJ/20 RBD retains binding compatibility with aminopeptidase N (APN) receptors from multiple species, including pig, human, dog, cat, and chicken, indicating broad host receptor adaptability. Docking simulations using sequence-reverted mutants suggested that these substitutions may slightly attenuate receptor-binding affinity, potentially influencing cross-species transmission. Notably, the N98K residue has been identified as a critical site involved in both APN binding and neutralizing epitopes, therefore, its mutation may influence receptor engagement and antigenic properties. In vivo virus infection experiments demonstrated that CH/HLJ/20 caused rapid disease onset and 100% mortality in neonatal piglets, with severe villous atrophy and high intestinal viral loads. These findings highlight the evolving genomic diversity, pathogenicity, and zoonotic potential of PDCoV, underscoring the critical importance of continuous viral surveillance, timely isolation and functional characterization of emerging strains, and enhanced understanding of cross-species transmission mechanisms to inform effective disease control and prevention strategies.
Coinfection with fowl adenovirus serotypes 1 and 4 (FAdV-1 and -4) enhances FAdV-4 replication through FAdV-1-mediated upregulation of HSPA2 expression.
Li X, Dan M, Liu D … +8 more , Ren B, Ge Y, Li Y, Hiscox JA, Stewart JP, Zhao Q, Liao M, Sun Y
Virulence · 2026 Dec · PMID 41408149 · Full text
Fowl adenoviruses (FAdVs) are widely distributed in poultry populations around the world, and many diseases are associated with FAdV infection in chickens. This study documented the first characterization of coinfection...
Fowl adenoviruses (FAdVs) are widely distributed in poultry populations around the world, and many diseases are associated with FAdV infection in chickens. This study documented the first characterization of coinfection with fowl adenovirus serotypes 1 and 4 (FAdV-1 and -4) associated with hydropericardium hepatitis syndrome (HHS) in Chinese layer flocks, revealing a novel viral cooperation mechanism. Two novel strains (CH/SX/201805-1 and -4) were identified and isolated, with whole-genome sequencing showing CH/SX/201805-1 clustering with FAdV-1 (99.7% identity to FAdV-A-61/11z), whereas CH/SX/201805-4 displayed characteristic ORF19/27/29 deletions mirroring emergent Chinese FAdV-4 variants. Experimental coinfection in SPF chickens resulted in 87.5% mortality, which was 16.7% greater than that resulting from infection alone, with exacerbated pathology. In vitro coinfection experiments demonstrated concurrent viral replication within same LMH cells, a previously unreported phenomenon, where FAdV-1 increased FAdV-4 replication efficiency 21-fold ( < 0.001). Transcriptomic profiling revealed heat shock protein A2 (HSPA2) as the most differentially expressed gene, which was upregulated 2.8-fold during coinfection compared with infection with FAdV-4 alone. Functional validation through HSPA2 knockdown reduced FAdV-4 replication, establishing that FAdV-1 potentiates FAdV-4 through HSPA2-mediated host modulation. These findings provide the first evidence of HSPA2-dependent interserotype synergy in FAdV and can be used to develop a cellular model for FAdV coinfection studies. These insights redefine the understanding of FAdV pathogenesis and create new avenues for targeted intervention strategies against emerging FAdV coinfections.
Cats are more susceptible to the prevalent H3 subtype influenza viruses than dogs.
Deng J, Ma C, Yu J … +3 more , Chen B, Li S, Zhou P
Virulence · 2026 Dec · PMID 41408147 · Full text
Recent reports have highlighted the increasing frequency of influenza A virus (IAV) spillover events from other species to dogs and cats. IAV, particularly the H3 subtype, exhibits a broad host range and a propensity for...
Recent reports have highlighted the increasing frequency of influenza A virus (IAV) spillover events from other species to dogs and cats. IAV, particularly the H3 subtype, exhibits a broad host range and a propensity for interspecies transmission, as exemplified by the sustained circulation of H3N2 and H3N8 canine influenza viruses in dog populations. This raises concerns about the potential role of companion animals as intermediate hosts in influenza virus transmission. To evaluate the susceptibility of dogs and cats to the prevalent H3 subtype influenza viruses, we experimentally inoculated groups of both species with three prevalent influenza viruses: H3N2 avian influenza virus (AIV), H3N8 avian influenza virus, and H3N2 swine influenza virus (SIV). Results showed that while all inoculated dogs exhibited seroconversion to all three viruses at 7, 14, and 21 days post-inoculation (dpi), they displayed no clinical signs, viral shedding, or evidence of viral replication in their organ tissues. In contrast, despite the cats did not exhibit apparent clinical signs, all inoculated cats exhibited seroconversion to all viruses at 7, 14 and 21 dpi, sustained nasal viral shedding for approximately one week, and demonstrated viral replication in their lungs, trachea, and nasal turbinate. Our findings underscore the higher susceptibility of cats compared to dogs to H3 subtype influenza viruses. These results emphasize the critical need for enhanced surveillance of cats within the influenza virus transmission network.
Auranofin potentiates linezolid activity against MRSA by disrupting redox homeostasis and inhibiting SarA-mediated virulence and biofilm.
Li JG, Zhong WC, Zhong LG … +6 more , Niu CY, Lu TY, Zhang CJ, Sun J, Liao XP, Zhou YF
Virulence · 2026 Dec · PMID 41400929 · Full text
Methicillin-resistant (MRSA) remains a major therapeutic challenge and poses a significant global health threat. Developing adjuvants to enhance the efficacy of existing antibiotics represents a promising strategy to ad...
Methicillin-resistant (MRSA) remains a major therapeutic challenge and poses a significant global health threat. Developing adjuvants to enhance the efficacy of existing antibiotics represents a promising strategy to address this issue. In this study, we evaluated auranofin as an adjuvant to potentiate the activity of linezolid against MRSA. Auranofin significantly increased MRSA susceptibility to linezolid, promoted intracellular linezolid accumulation, and suppressed the emergence of MRSA resistance to linezolid. Mechanistically, auranofin inhibited the Trx/TrxR system, inducing redox imbalance and reactive oxygen species (ROS) accumulation, which triggers DNA damage and transcriptional dysregulation. Auranofin synergized with linezolid to achieve dual inhibition of MRSA protein synthesis. Furthermore, auranofin downregulated the global regulator , impaired SarA DNA-binding activity, and enhanced SarA phosphorylation, thereby attenuating SarA-mediated virulence factors (eg, adhesins and toxins) and biofilm formation. Importantly, auranofin fully restored anti-MRSA activity of linezolid in both and murine bacteremia models. Collectively, these findings identify auranofin as a promising adjuvant to linezolid and highlight its potential to improve therapeutic outcomes against invasive MRSA infections.
Cell fusion-related proteins regulate hyphal fusion, conidiation, trap morphogenesis, and secondary metabolism in .
Liu Q, Duan S, Luo H … +4 more , Yuan H, Chen S, Zhang H, Yang J
Virulence · 2026 Dec · PMID 41400923 · Full text
The diverse mycelial networks of fungi are generated through polar growth, cell division, and cell fusion. Most of the genes are well characterized as crucial for cellular communication and fusion processes in filamentou...
The diverse mycelial networks of fungi are generated through polar growth, cell division, and cell fusion. Most of the genes are well characterized as crucial for cellular communication and fusion processes in filamentous fungi, but their functions and molecular mechanisms remain poorly understood. Here, we functionally characterized the hyphal anastamosis protein 4 (AoHam4), hyphal anastamosis-8 protein (AoHam8) and serine/threonine protein phosphatase 2A (AoPP2A) in the model nematode-trapping fungus . Our results indicate that , and genes are essential for hyphal fusion and trap morphogenesis, and modulate mycelial growth, conidial production, and pathogenicity in . Staining, RT-qPCR and transmission electron microscopy (TEM) results indicated that all three genes are involved in regulating reactive oxygen species (ROS) accumulation, lipid metabolism and autophagy processes. Moreover, RNA-Seq and liquid chromatography-mass spectrometry (LC-MS) experiments further confirmed that deletion of , and genes affects transcription and metabolic levels. Yeast-two-hybrid (Y2H) analysis showed that AoPP2A can interact with AoSO (Soft, a fungus-specific scaffolding protein, is involved in signaling and secretion with the MAK-2 cascade). Since the Δ mutant strain was more sensitive to cell wall-disrupting reagents, speculating that may regulate the mitogen-activated protein (MAP) kinase cascade response by activating the cell wall integrity pathway. Collectively, our studies illuminate the crucial roles of the fungal cell-fusion genes , and in a, as well as laying the groundwork for clarifying the mechanisms of mycelial development and trap morphogenesis of nematode-trapping fungi.
Cleavage of cellular substrate porcine gasdermin D by porcine torovirus 3C-like protease induces pyroptosis.
Pan D, Liu XE, Hong X … +11 more , Liu Y, Yin PF, Zeng JW, Lv Q, Du EZ, Fan W, Yang YL, Shi F, Wang B, Dong B, Huang YW
Virulence · 2026 Dec · PMID 41400836 · Full text
Torovirus (ToV), while resembling coronavirus (CoV), belongs to a distinct family in the order . Porcine ToV (PToV) is widespread in pig populations across many countries, yet its potential pathogenicity in pigs remains...
Torovirus (ToV), while resembling coronavirus (CoV), belongs to a distinct family in the order . Porcine ToV (PToV) is widespread in pig populations across many countries, yet its potential pathogenicity in pigs remains poorly understood. The viral 3C-like protease (3CLP) plays a crucial role in processing viral polyproteins and manipulating the host antiviral immune response by targeting cellular proteins through its catalytic activity. In this study, we focused on PToV 3CLP due to its unique catalytic dyad characteristics and substrate recognition properties, which are distinct from those of CoV 3CLPs. We revealed that PToV 3CLP induces pyroptosis in porcine small intestinal IPEC-J2 cells and further demonstrated that porcine gasdermin D (pGSDMD) is a cleavage substrate for PToV 3CLP associated with this process. The catalytic residues, histidine 53 and serine 160, essential for the protease activity of PToV 3CLP, were required for the cleavage of pGSDMD at two distinct sites, glutamine 193 (Q193) and glutamine 277 (Q277). One of fragments produced by PToV 3CLP cleavage, pGSDMD, mimicked the activity of the N-terminal domain of pGSDMD (pGSDMD) in forming pores and ultimately triggering pyroptosis. Intriguingly, these results contrast with the inhibitory effect of CoV 3CLPs on pyroptosis, previously reported to target pGSDMD at the Q193 site. The study provides additional evidence of the distinct nature of 3CLP between ToV and CoV, which may partly explain the divergent clinical manifestations and pathogenesis observed in pigs infected by these nidoviruses.
Adult duck fecal microbiota transplantation alleviates short beak and dwarfism syndrome in ducklings by inhibiting Th17 cell differentiation.
Liu M, Liu W, Zhao K … +5 more , Zhang W, Lei B, Zhang Y, Li L, Yuan W
Virulence · 2026 Dec · PMID 41400824 · Full text
Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal f...
Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal flora of ducklings through fecal microbiota transplantation from adult ducks (FMT-A) can alleviate SBDS is an interesting question. This study aimed to investigate the impact of FMT-A on the susceptibility of ducklings to NGPV infection, to elucidate the potential relationship between gut microbiota and viral pathogenicity. The results showed that ducklings were more susceptible to NGPV than adults, and that adult ducks exhibited higher fecal microbiota richness and diversity. FMT-A treatment attenuated NGPV-induced reductions in body weight, beak and tibia length, and muscle mass. Furthermore, FMT-A alleviated gut dysbiosis and intestinal tissue damage, increased glycogen in the intestinal mucosa, upregulated ZO-1 expression, expanded the epiphyseal region, and reduced osteoclast numbers in the tibia of ducklings. Moreover, FMT-A suppressed the expression of the Th17 cell-specific transcription factor retinoic acid receptor-related orphan receptor γt in the ileum and bone, and decreased the expression levels of pro-inflammatory cytokines in the ileum, bone, and serum. These findings indicate that ducklings are more susceptible to NGPV than adult ducks, with significantly lower diversity and abundance of fecal microbiota. FMT-A can stabilize intestinal flora, mitigate intestinal barrier damage, inhibit Th17 cell differentiation, thereby reducing abnormal bone development, and ultimately alleviate SBDS in ducklings. These findings provide a theoretical basis for developing novel strategies targeting gut microbiota modulation to prevent and control SBDS in ducklings.
Apparent expansion of virulent in humans and sea otters.
Sebastian PJ, Schlesener C, Byrne BA … +9 more , Miller M, Smith W, Batac F, Burek-Huntington K, Goertz CEC, Rouse N, Hunter N, Weimer BC, Johnson CK
Virulence · 2026 Dec · PMID 41399136 · Full text
Vibriosis is the most important public health threat from seafood consumption and marine recreation. Pathogenic spp. employ virulence factors, including hemolysins and secretion systems, frequently detected in human cas...
Vibriosis is the most important public health threat from seafood consumption and marine recreation. Pathogenic spp. employ virulence factors, including hemolysins and secretion systems, frequently detected in human cases, but virulence data in northern and southern sea otters ( and . nereis, respectively) are limited despite their potential as marine bioindicators. Genomic epidemiology was used to characterize virulence factors of spp. genomes ( = 570), including ( = 55), ( = 52), non-O1/O139 ( = 163), and ( = 287) collected in North America (2000-2019). Virulence factors of were compared between isolation sources: bivalves, environment, humans, and southern and northern sea otters. Hemolysins (, ) and type III secretion system 2 (T3SS2) gene prevalences were lowest in environmental isolates, while and T3SS2 gene prevalences were higher in human and northern sea otter isolates than those from southern sea otters. A hemolysin allele () was detected almost exclusively in human and sea otter isolates. Despite genomic diversity, detected genomic clusters were comprised of highly related and / genomes from nonenvironmental sources including humans and sea otters. Observed pathology in spp. positive sea otters frequently included septicemia, enteritis, and moderate-to-severe melena. Co-occurrence of T3SS2 and T6SS1 in was associated with pathological findings and ampicillin-susceptible genotypes, suggesting a trade-off between virulence and antimicrobial resistance. Based on these findings, undergoes selection pressures resulting in apparent expansion, i.e. genomic clustering, of / virulent strains infecting humans and sea otters.
Genome-wide Identification of conditionally essential genes supporting growth in serum and cerebrospinal fluid.
Juanpere-Borras M, Zhao T, Boekhorst J … +6 more , Fernandez-Ciruelos B, Sanyal R, Arifa N, Wagenaar T, van Baarlen P, Wells JM
Virulence · 2026 Dec · PMID 41396007 · Full text
is a major cause of sepsis and meningitis in pigs, and zoonosis through the emergence of disease-associated lineages. The ability of to adapt and survive in host environments, such as blood and cerebrospinal fluid (CSF)...
is a major cause of sepsis and meningitis in pigs, and zoonosis through the emergence of disease-associated lineages. The ability of to adapt and survive in host environments, such as blood and cerebrospinal fluid (CSF), is important for pathogenesis. Here, we used Transposon Sequencing (Tn-seq) coupled with Nanopore sequencing to identify conditionally essential genes (CEGs) for the growth of P1/7 in active porcine serum (APS) and CSF derived from choroid plexus organoids. To our knowledge, this is the first successful application of ONT to Tn-library screening, enabling rapid local runs and a publicly available analysis pipeline. Through comparative fitness analyses, we identified 33 CEGs that support growth in APS and 25 CEGs in CSF. These genes highlight the importance of pathways related to amino acid transport, nucleotide metabolism, and cell envelope integrity. Notably, the LiaFSR regulatory system and multiple ABC transporters were important for proliferation. We also identified several genes of unknown function as essential for growth, pointing to previously unrecognized genetic factors involved in adaptation during infection. These findings provide new insights into the genetic requirements for survival in host-like environments and a deeper understanding of its ability to adapt to distinct physiological niches.
Microsporidia keratoconjunctivitis identified as an emerging zoonotic threat from pet parrots: Clinical and metagenomic next-generation sequencing evidence.
Sun Z, Zhang P, Li Y … +5 more , Zhang C, Liu Y, Ma B, Lan Q, Qi H
Virulence · 2026 Dec · PMID 41395987 · Full text
Microsporidia are opportunistic, obligate intracellular fungi capable of causing keratoconjunctivitis. Because the clinical manifestations of microsporidia keratoconjunctivitis are indistinguishable from those of other e...
Microsporidia are opportunistic, obligate intracellular fungi capable of causing keratoconjunctivitis. Because the clinical manifestations of microsporidia keratoconjunctivitis are indistinguishable from those of other etiologies, and the organism is difficult to culture, its diagnosis is challenging. The transmission routes of microsporidia keratoconjunctivitis remain poorly defined, and zoonotic sources have long been suspected but rarely confirmed. Between September 2024 and October 2025, a total of 15 confirmed cases of microsporidia keratoconjunctivitis were identified at Peking University Third Hospital. The diagnosis was established based on Giemsa-stained corneal scrapings and/or metagenomic next-generation sequencing (mNGS) of conjunctival lavage samples. Among these 15 patients, microsporidia spores were observed in corneal scrapings from nine individuals, while 13 tested positive for () by mNGS. Notably, all affected patients reported a history of parrot exposure. Self-reported parrot exposures included direct ocular contact ( = 3) and indirect contact ( = 12). Six patients reported that their parrots had exhibited ocular abnormalities and diarrhea before the onset of the patients' symptoms, and two patients stated that their parrots had died prior to their clinical presentation. Ocular and fecal samples from three parrots associated with four patients were collected, and all the parrots tested positive for by mNGS. These findings provide both clinical and molecular evidence supporting pet parrots as a zoonotic source of microsporidia keratoconjunctivitis. This emerging zoonotic threat calls for greater clinical awareness and attention to animal exposure history during diagnosis.
Autophagy and ubiquitination in important swine viral infections: Host defense and viral antagonism.
He Z, Liu M, Xie Q … +2 more , Lu H, Guo C
Virulence · 2026 Dec · PMID 41395986 · Full text
Swine viral infections continue to impose major economic and animal-health burdens worldwide, with pathogens such as porcine epidemic diarrhea virus (PEDV), African swine fever virus (ASFV), and porcine reproductive and...
Swine viral infections continue to impose major economic and animal-health burdens worldwide, with pathogens such as porcine epidemic diarrhea virus (PEDV), African swine fever virus (ASFV), and porcine reproductive and respiratory syndrome virus (PRRSV) causing recurrent outbreaks. Autophagy and ubiquitination are central degradative pathways that act as double-edged swords, serving both host defense and viral exploitation. In this narrative review, we synthesize recent advances showing how these pathogens manipulate ubiquitin - autophagy circuits while host cells counteract through selective autophagy. We propose an autophagy - metabolism - immunity triad that positions autophagy as a hub linking infection, metabolic reprogramming, and immune evasion. This integrated framework moves beyond the traditional view of autophagy as strictly antiviral or pro-viral. Deciphering how viruses hijack ubiquitin - autophagy axes reveals actionable therapeutic targets and translational opportunities for antivirals, adjuvants, and metabolic interventions to reduce the burden of swine viral diseases.
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