Virulence[JOURNAL]
Sun
200 papers
alleviates infection in mice while modulating secondary bile acids.
Zhao M, Wen B, Ouyang Z … +8 more , Yang J, Yang H, Zhao J, Qiang C, Wang W, Qin P, Niu Y, Zhao J
Virulence · 2026 Dec · PMID 42402046 · Publisher ↗
infection (CDI) is a major cause of antibiotic-associated diarrhea, with frequent recurrences closely linked to antibiotic-induced dysbiosis of the gut microbiota and bile acid metabolism. , a potential probiotic capable...
infection (CDI) is a major cause of antibiotic-associated diarrhea, with frequent recurrences closely linked to antibiotic-induced dysbiosis of the gut microbiota and bile acid metabolism. , a potential probiotic capable of converting primary to secondary bile acids, has shown therapeutic promise in several metabolic and inflammatory diseases. This study evaluated the preventive and therapeutic effects of against CDI and explored the underlying mechanisms. We characterized the probiotic properties of four strains and investigated the inhibitory activity of strain 1190003 against , as well as its protective and therapeutic efficacy in mouse models. Gut microbiota structure and bile acid metabolic profiles were analyzed by integrating 16S rRNA gene sequencing and metabolomics. The four strains exhibited strong acid and bile salt tolerance as well as auto-aggregation ability. Supernatants from co-cultured with cholic acid (4 mM and 8 mM) significantly inhibited growth, toxin expression and spore formation, with deoxycholic acid identified as the key inhibitory metabolite. Both live and its culture supernatant alleviated disease severity in CDI mouse models and ameliorated gut microbiota dysbiosis. Notably, the relative abundance of was increased following supernatant treatment. Furthermore, intervention with either live or its supernatant elevated the level of hyodeoxycholic acid. In summary, acts as a potential probiotic that alleviates CDI by ameliorating gut microbiota dysbiosis and remodeling bile acid metabolism. These findings provide experimental evidence for its use as a microbiota-based therapeutic strategy.
Identification and profiling of HLA-A*02:01-restricted peptides through immunopeptidomics in HLA-A2.1 transgenic mice.
Liang R, Luo X, Xia W … +8 more , Gu H, Li D, Gao Y, Zuo Z, Gao F, Ding J, Tang X, Li Z
Virulence · 2026 Dec · PMID 42402043 · Publisher ↗
HLA class I presentation of pathogen-derived peptides is essential for CD8+ T-cell recognition of . While MHC ligands have been documented, the ligandome during infection progression remains poorly characterized. Here,...
HLA class I presentation of pathogen-derived peptides is essential for CD8+ T-cell recognition of . While MHC ligands have been documented, the ligandome during infection progression remains poorly characterized. Here, we employed an MS-based immunopeptidomics approach to directly profile the immunopeptidome presented by HLA-A *02:01 in transgenic mice. By employing a hierarchical discovery funnel, our analysis identified a comprehensive repertoire of 3,744 unique -derived peptides. Subsequent filtering for canonical 8-12mers, matching the typical binding length for HLA-A *02:01 ligands, established a high-confidence foundational ligandome of 3,433 peptides. Source protein analysis revealed that these peptides originate from diverse parasite proteins, including a substantial proportion of previously uncharacterized hypothetical proteins. Notably, specific ligands were consistently detected across both acute and chronic stages, suggesting stable MHC-I presentation throughout the infection cycle. By integrating predictions with experimental validation, we prioritized 73 high-affinity candidates, five of which exhibited robust HLA-A *02:01 binding capacity and . Specifically, we identified a novel ligand derived from glycogen synthase (PGS) and determined its co-crystal structure with HLA-A *02:01, revealing favorable binding architecture. Overall, these findings expand the known HLA-A *02:01-restricted ligand landscape of and provide a high-priority list of candidates for future functional validation of CD8+ T-cell immunogenicity.
Encephalomyocarditis virus impairs the blood-brain barrier by degrading tight junction proteins via AKT3-dependent autophagic and apoptotic pathways.
Dou X, Wang N, Yao S … +9 more , Chen X, Li S, Xie J, Li X, Yang Y, Wen Y, Idris A, Li H, Feng R
Virulence · 2026 Dec · PMID 42397844 · Publisher ↗
Encephalomyocarditis virus (EMCV) infection causes viral encephalitis; however, the mechanisms underlying blood-brain barrier (BBB) disruption remain poorly understood. Here, we demonstrate that EMCV actively replicates...
Encephalomyocarditis virus (EMCV) infection causes viral encephalitis; however, the mechanisms underlying blood-brain barrier (BBB) disruption remain poorly understood. Here, we demonstrate that EMCV actively replicates in mouse brain tissue, induces robust neuroinflammation characterized by elevated proinflammatory cytokines and chemokines, and markedly increases BBB permeability as evidenced by Evans blue and sodium fluorescein extravasation. Importantly, tight junction (TJ) proteins ZO-1 and Occludin are selectively degraded at the post-transcriptional level, whereas Claudin-5 expression remains stable. Consistently, in vitro BBB models confirmed EMCV traversal, reduced transendothelial electrical resistance, and TJ disruption. Mechanistically, EMCV induces biphasic PI3K/AKT modulation and specifically downregulates AKT3. Notably, AKT3 knockdown exacerbates both autophagy and apoptosis, thereby accelerating ZO-1 and Occludin degradation while promoting viral replication. Furthermore, pharmacological inhibition of autophagy (chloroquine) or apoptosis (Z-VAD-FMK) effectively rescues TJ proteins and reduces viral load. Interestingly, the Caspase-8 inhibitor Z-IETD-FMK provides the most robust protection, implicating the extrinsic apoptotic pathway as the dominant route. Collectively, EMCV sequentially activates non-redundant AKT3-dependent autophagic and apoptotic pathways to degrade TJ proteins, ultimately enabling viral traversal across the compromised BBB and offering therapeutic targets for viral encephalitis.
A secreted AIP-Like peptide from inhibits the Agr quorum sensing system of .
Daher R, Francois P, Vincentelli R … +7 more , Vergunst AC, Grenga L, Pouget C, Boyer J, Gaïa N, Lavigne JP, Dunyach-Remy C
Virulence · 2026 Dec · PMID 42397843 · Publisher ↗
is a major human pathogen whose virulence is tightly regulated by the Agr quorum sensing system. In this study, we investigated the impact of Adh2, a secreted protein from the commensal bacterium , on physiology and pat...
is a major human pathogen whose virulence is tightly regulated by the Agr quorum sensing system. In this study, we investigated the impact of Adh2, a secreted protein from the commensal bacterium , on physiology and pathogenicity. Adh2 shares structural similarity with native auto-inducing peptides (AIPs), including the conserved CDFIM motif characteristic of Agr group I. We hypothesized that Adh2 interferes with Agr signaling by competitively binding the AgrC receptor. Exposure to Adh2 significantly repressed and its downstream α-hemolysin , while upregulating , a gene encoding a surface adhesin. Deletion of an Adh2 region encompassing the conserved CDFIM motif abolished this regulatory effect, indicating that this region is required for Adh2 activity. RNA-Seq analysis revealed global transcriptional reprogramming, with downregulation of virulence and metabolic genes. Proteomic profiling corroborated these findings, showing reduced abundance of proteins involved in metabolic pathways (e.g. carbohydrate, lipid, and nucleotide metabolism), consistent with a shift toward a low-energy, colonization-oriented state. Importantly, Adh2 did not impair growth across a wide concentration range (0.01-10 g/L) but significantly enhanced biofilm formation. , Adh2 administration significantly improved survival in zebrafish embryos infected with , validating its anti-virulence potential. Together, these findings demonstrate that Adh2 suppresses Agr signaling and virulence gene expression while promoting a persistent phenotype. By shifting toward a metabolically reduced and less pathogenic state, Adh2 emerges as a promising candidate for therapeutic modulation of bacterial behavior, particularly in the context of chronic wound infections.
Correction.
Virulence · 2026 Dec · PMID 42388059 · Publisher ↗
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Landscape of the upper and lower airway microbiota in children with community-acquired pneumonia.
Luo Y, Zhu L, Xu H … +10 more , Li D, Zhu Y, Xiong J, Li L, Guo Y, Yi K, Wang Z, Xue Z, Zhao D, Liu F
Virulence · 2026 Dec · PMID 42388029 · Publisher ↗
Community-acquired pneumonia (CAP) is one of the most common causes of death in children. Obtaining lower airway samples from children with CAP has so far remained challenging. This multicenter study enrolled 198 childre...
Community-acquired pneumonia (CAP) is one of the most common causes of death in children. Obtaining lower airway samples from children with CAP has so far remained challenging. This multicenter study enrolled 198 children with CAP indicated for fiberoptic bronchoscopy. Nasopharyngeal aspirates and bronchoalveolar lavage fluid (BALF) were collected for targeted next-generation sequencing (tNGS) and 16S ribosomal RNA (rRNA) sequencing to compare the pathogens and microbiota. Firstly, diversities of the microbiota between the upper and lower airways were compared. Then, diversities of the lower airway microbiota were analyzed among different pathogen groups and outcome groups. The high consistency was observed between the first pathogen detected in the upper and lower airways of children with CAP by tNGS. Diversity indices were higher in the upper airways than in the lower airways in children with CAP. The upper airway richness indices were higher in the group with consistent top pathogens between the upper and lower airways. infection was related to the reduced diversity of the lower airway microbiota compared to Bacteria and Virus groups. The oxygen group showed higher abundance of , with being the most representative microbiota in this group.
Divergent virulence and serological profiles reveal pathogenic evolution within the genus.
Li C, Shen S, Fu L … +8 more , Ni J, Xiao J, Qian J, Chen S, Fang Y, Zhou M, Deng F, Wu X
Virulence · 2026 Dec · PMID 42384674 · Publisher ↗
Viruses within the genus ( family), phylogenetically divided into SFTSV and Bhanja groups, pose public health risks through cross-species transmission. Despite their significance, a systematic comparison of their infect...
Viruses within the genus ( family), phylogenetically divided into SFTSV and Bhanja groups, pose public health risks through cross-species transmission. Despite their significance, a systematic comparison of their infectivity, pathogenicity, and antigenicity is lacking. This study evaluates these key properties for five representative species: Severe fever with thrombocytopenia syndrome virus (SFTSV), Guertu virus (GTV), and Heartland virus (HRTV) from the SFTSV group; and Bhanja virus (BHAV) and Lone Star virus (LSV) from the Bhanja group. The five bandaviruses demonstrated efficient replication kinetics across a panel of human and mammalian cell lines, suggesting a broad cellular tropism. Wild-type C57BL/6 mice developed transient viremia (2-10 dpi) without overt disease, followed by neutralizing antibody production. Cross-neutralization was robust within each phylogenetic group but restricted between groups, supporting two separate serogroups. In contrast, IFNAR C57BL/6 mice exhibited significant hematological abnormalities and uniformly lethal infection, with the 50% lethal dose-based virulence ranking as SFTSV > LSV > GTV >BHAV >HRTV. Pathological analysis revealed that SFTSV caused severe multi-organ damage, with predominant spleen tropism; GTV and HRTV induced similar but milder spleen-tropic lesions; and LSV and BHAV caused multi-organ injuries primarily affecting the liver and spleen. Our findings demonstrate that the variation in virulence among species is closely linked to their antigenic divergence and evolutionary lineages. The established infection models provide valuable platforms for investigating virus-host interactions and pathogenesis. These insights facilitate the development of vaccines and antiviral therapies, and improve public health preparedness against emerging tick-borne pathogens.
Piperine reverses colistin resistance in multidrug resistant Gram-negative pathogens by membrane disruption and ROS damage.
Zhang J, Liu Q, Shao H … +7 more , Feng M, Li Z, Feng Y, Wu H, He D, Zhai Y, Hu GZ
Virulence · 2026 Dec · PMID 42381184 · Publisher ↗
The global spread of colistin (COL) resistance, particularly mediated by , threatens the efficacy of this last-line antibiotic against multidrug-resistant (MDR) Gram-negative pathogens. This development underscores the u...
The global spread of colistin (COL) resistance, particularly mediated by , threatens the efficacy of this last-line antibiotic against multidrug-resistant (MDR) Gram-negative pathogens. This development underscores the urgency of developing innovative therapeutic strategies to counteract antimicrobial resistance mechanisms. This study demonstrates that piperine (PIP), a natural alkaloid, functions as a potent adjuvant that restores COL efficacy through a multi-target mechanism. The combination of PIP and COL exhibits significant synergism against clinically relevant pathogens, including -positive strains (FICI: 0.07-0.281), and was not susceptible to the development of drug resistance. Additionally, this combination effectively inhibits and eradicates biofilms. Mechanism studies and omics analysis confirmed that PIP combined with COL could cause bacterial membrane disruption, proton motive force (PMF) disruption, efflux pumps inhibition, resulting in accumulation of bacterial reactive oxygen species (ROS) and finally cell death. Furthermore, PIP suppresses MCR-1 through dual suppression of gene expression and protein function. The therapeutic potential was confirmed in murine infection models, where the combination significantly improved survival rates, reduced bacterial loads, and attenuated inflammatory responses. This study provides the first comprehensive elucidation of the multi-target synergy between COL and PIP, offering a promising therapeutic strategy that simultaneously overcomes existing resistance and impedes resistance development.
Bridging environmental pollution and immune dysregulation: How microplastics disrupt gut homeostasis to promote allergic diseases.
Zhang X, Liu K, Zhang Z … +5 more , Huang X, Liu M, Bai D, Yang R, Yang C
Virulence · 2026 Dec · PMID 42381177 · Publisher ↗
Parallel increases in microplastic (MP) pollution and allergic diseases suggest an environmental link in allergy pathogenesis. While intestinal barrier dysfunction and dysbiosis are hallmark features of allergic diseases...
Parallel increases in microplastic (MP) pollution and allergic diseases suggest an environmental link in allergy pathogenesis. While intestinal barrier dysfunction and dysbiosis are hallmark features of allergic diseases, the mechanisms by which persistent MPs drive these processes remain unclear. This review proposes a mechanistic pathway where orally ingested MPs disrupt the intestinal barrier through physical and chemical toxicity, precipitating functional dysbiosis. Specifically, MPs suppress key short-chain fatty acid (SCFA)-producing commensals. The resulting SCFA deficit impairs the "gut-airway axis," weakening respiratory immune tolerance and increasing allergen susceptibility. We further argue for integrating gut health assessments into standardized allergy diagnostics and treatments. Despite this novel perspective, significant knowledge gaps remain regarding causality, dose-response relationships, and specific biomarkers. Addressing these challenges is critical for translating scientific findings into public health policies and clinical interventions to mitigate the rising global burden of allergic diseases.
Genomic epidemiology, evolution, and transmission dynamics of porcine sapelovirus associated with diarrheic piglets.
Li X, Ma XA, Wang X … +6 more , Li Q, Yuan Q, Wang J, Bai H, Liu Y, Zhao F
Virulence · 2026 Dec · PMID 42374704 · Full text
Porcine sapelovirus (PSV) is increasingly detected in swine enteric disease complexes, but its evolutionary dynamics and transmission patterns remain insufficiently characterized. In this study, we analyzed 327 fecal sam...
Porcine sapelovirus (PSV) is increasingly detected in swine enteric disease complexes, but its evolutionary dynamics and transmission patterns remain insufficiently characterized. In this study, we analyzed 327 fecal samples collected from diarrheic piglets between 2015 and 2022 and identified persistent PSV detection in northeastern China. Because PSV was detected in the context of mixed enteric viral infections in this dataset, our data do not establish PSV as an independent causative agent of diarrhea. Comparative whole-genome and evolutionary analyses of globally circulating PSV strains revealed substantial genetic diversity, with higher apparent short-term substitution-rate estimates observed in the African and Japanese datasets. In China, inter-strain genetic recombination appeared to represent an additional driver of viral diversification. Temporal evolutionary analyses indicated a dynamic and complex evolutionary landscape within China. Phylogeographic reconstruction identified multiple putative transmission nodes within the currently available genome dataset, suggesting broad geographic dissemination of PSV lineages but not definitive source-sink relationships. These findings enhance our understanding of PSV genomic epidemiology and provide useful information for molecular surveillance of PSV and other diarrhea-associated viruses in swine populations.
Hijacking and subversion of macrophage antiviral functions by viruses.
Xu Z, Shi F, Han J … +2 more , Zhou L, Yang H
Virulence · 2026 Dec · PMID 42370645 · Full text
Macrophages are frontline effectors of innate immunity, acting as essential elements for clearing pathogens. However, viruses have continuously evolved sophisticated mechanisms to subvert these critical defenses. This re...
Macrophages are frontline effectors of innate immunity, acting as essential elements for clearing pathogens. However, viruses have continuously evolved sophisticated mechanisms to subvert these critical defenses. This review comprehensively decodes how viral pathogens systematically dismantle macrophage microbicidal capacities. It delineates the evasion of pattern recognition receptor surveillance, the hijacking of endocytic trafficking, and the active arrest of phagolysosomal maturation to secure intracellular replication niches. Furthermore, the review explores the paradoxical viral manipulation of the host oxidative burst, where pathogens weaponize reactive oxygen species or exploit antioxidant machineries, driving severe redox dysregulation. Profound metabolic reprogramming, including shifts toward aerobic glycolysis and the skewing of inflammatory polarization alongside cell death pathways, is also examined. Ultimately, these evasion strategies inflict functional paralysis on macrophages, heavily predisposing hosts to severe secondary bacterial coinfections. Mapping this virus-host crosstalk highlights critical vulnerabilities, providing a foundation for novel host-directed antiviral immunotherapies.
Virulence attenuation in ST11-K64 explains its divergent clinical manifestation from ST23-K1.
Li S, Zhang Y, Zeng Q … +9 more , Zheng L, Yan J, Wang Y, Liu Y, Yu L, Li Y, Li M, Feng J, Jiang X
Virulence · 2026 Dec · PMID 42359816 · Full text
The clinical threat posed by is dual-faceted, encompassing both hypervirulence and carbapenem resistance. The emergence of hypervirulent carbapenem-resistant (hv-CRKP) merges these threats, with the ST11-K64 clone bein...
The clinical threat posed by is dual-faceted, encompassing both hypervirulence and carbapenem resistance. The emergence of hypervirulent carbapenem-resistant (hv-CRKP) merges these threats, with the ST11-K64 clone being a dominant and concerning lineage. However, its clinical presentation diverges from the classic hypervirulent (hvKp); hv-CRKP is isolated from respiratory sites but is notably absent from pyogenic liver abscesses. This distinct clinical niche prompted us to investigate the underlying pathogenicity differences. Among 847 clinical isolates, 157 (18.5%) were identified as hv-CRKP. From this hv-CRKP collection, we selected five representative ST11-K64 isolates for downstream phenotypic and mechanistic analyses. Despite its prevalence and multidrug resistance, the ST11-K64 clone exhibited significantly attenuated lethality in mouse models compared to ST23-K1. Crucially, in a murine intestinal colonization model that mimics natural infection, only ST23-K1 successfully colonized the gut, caused bacteremia, and formed liver abscesses. In contrast, ST11-K64 strains showed impaired intestinal colonization and failed to translocate to the liver. Phenotypic profiling showed reduced capsule viscosity and siderophore production in ST11-K64 relative to ST23-K1, accompanied by diminished macrophage and Kupffer cell-associated fitness. RT-qPCR identified higher expression of , , and in ST23-K1, and isogenic deletion and complementation of or in the ST23-K1 background supported their contribution to capsule/siderophore-associated phenotypes and intracellular survival in RAW264.7 macrophages. Together, these results indicate that while ST11-K64 hv-CRKP represents a serious antimicrobial-resistance threat, its invasive pathogenicity is route- and context-dependent and does not fully recapitulate the classic entero-hepatic hypervirulence of ST23-K1.
Nucleotide variations in 3' untranslated region contribute to the enhanced virulence and replication efficiency of reemerging Japanese encephalitis virus genotype V.
Xia Q, Zhang Y, Zheng J … +7 more , Liu K, Li B, Li Z, Shao D, Qiu Y, Ma Z, Wei J
Virulence · 2026 Dec · PMID 42357978 · Full text
Japanese encephalitis virus, a major causative agent of viral encephalitis in Asia, is classified into five genotypes. Genotype V (GV) has reemerged after more than 50 years of apparent absence, following identification...
Japanese encephalitis virus, a major causative agent of viral encephalitis in Asia, is classified into five genotypes. Genotype V (GV) has reemerged after more than 50 years of apparent absence, following identification of the sole GV isolate - the Muar strain - in 1952. Newly reemerged GV strains are genetically distinct from the ancestral Muar strain. In this study, we compared virulence and replication efficiency between the newly reemerged XZ0934 strain and the ancestral Muar strain. Viral titers in cultured cells, as well as viremia and mortality in mice infected with the XZ0934 strain, were significantly higher than those observed with the Muar strain, indicating enhanced virulence and replication efficiency of the XZ0934 strain. Multiple nucleotide variations in the 3' untranslated region (3'UTR) were identified between the XZ0934 and Muar strains; such variations contributed to the increased virulence and replication efficiency of the XZ0934 strain. These nucleotide variations resulted in substantial differences in the stem - loop (SL) I, SLII, and 3'SL structures of the 3'UTR and led to differential production of subgenomic flaviviral RNA (sfRNA). The variations also were responsible for differential inhibition of type I interferon production and between the two strains. These effects collectively contributed to the enhanced virulence and replication efficiency of the XZ0934 strain relative to the Muar strain. Our findings provide insight into the role of genetic variation in determining virulence and replication efficiency between newly reemerged and ancestral GV strains, as well as the molecular basis underlying GV virus reemergence.
Bovine coronavirus enters PBIECs via membrane fusion and clathrin-, caveolin-mediated endocytosis, macropinocytosis.
Chen C, Su N, Zhao L … +7 more , Li N, Ma Z, Luo B, Liu W, Song B, Zhang L, Guo K
Virulence · 2026 Dec · PMID 42334091 · Full text
Bovine coronavirus (BCoV) is an important pathogen that exhibits dual tropism for the respiratory and intestinal tracts, causing winter dysentery in adult cattle, diarrhea and respiratory infections in calves, thus impos...
Bovine coronavirus (BCoV) is an important pathogen that exhibits dual tropism for the respiratory and intestinal tracts, causing winter dysentery in adult cattle, diarrhea and respiratory infections in calves, thus imposing considerable economic losses on the global cattle industry. Our previous studies demonstrated that BCoV gains entry into susceptible HRT-18 cells through membrane fusion and clathrin-mediated endocytosis (CME). However, the precise mechanisms by which BCoV enters host cells remain incompletely elucidated, particularly in primary bovine intestinal epithelial cells (PBIECs). Importantly, as primary cells derived from the natural host, PBIECs more closely recapitulate the in infection microenvironment than HRT-18 cell lines. In the present study, chemical inhibitors, RNA interference, and fluorescently labeled BCoV particles were used to define distinct entry pathways. Our data demonstrated that BCoV enters PBIECs via membrane fusion and three distinct endocytic pathways, including CME, caveolin-mediated endocytosis (CavME), and macropinocytosis. Dynamin, microtubules, cathepsins, and an acidic environment are essential for mediating endocytic entry, whereas cholesterol and TMPRSS2 are dispensable for this process. Furthermore, targeted interference with Rab5, Rab7, and Rab11 suppressed BCoV entry into PBIECs. Consistently, co-localization of fluorescently labeled BCoV with Rab5, Rab7, and Rab11 was observed by confocal microscopy, indicating that these Rab GTPases are involved in BCoV entry into PBIECs. These findings elucidate the entry mechanisms of BCoV and provide novel perspectives to enhance a more comprehensive understanding of the BCoV life cycle.
The current landscape and future directions of Lyme disease vaccines.
Chen Z, He L, Huang X … +3 more , Liang X, Liu A, Bao F
Virulence · 2026 Dec · PMID 42324826 · Full text
Lyme disease (LD) represents a significant public health challenge in North America and Eurasia. The persistent increase in its incidence may create an opportunity for vaccines to gain broader acceptance. Recent years ha...
Lyme disease (LD) represents a significant public health challenge in North America and Eurasia. The persistent increase in its incidence may create an opportunity for vaccines to gain broader acceptance. Recent years have seen notable advances in vaccine development. However, achieving a balance between broad-spectrum protection and durable immunity remains a critical bottleneck. This article is presented as a narrative review that systematically summarizes recent progress in Lyme disease vaccine research worldwide, with particular emphasis on the strengths and limitations of approved and investigational candidates. Unlike existing reviews, this study integrates recent clinical investigations of multivalent vaccine candidates with breakthrough advances across diverse vaccine platforms, yielding a comprehensive and current synthesis. We identify critical challenges in contemporary vaccine development and propose actionable solutions. Our forward-looking perspective centers on a triangular strategy that integrates antigen multivalency, platform personalization, and geographical customization, providing a conceptual framework to guide future LD immunoprophylaxis research.
proteomic response to infection with .
Abt-Becker C, Burzlaff J, Mikkat S … +2 more , Kreikemeyer B, Patenge N
Virulence · 2026 Dec · PMID 42312742 · Full text
is considered a suitable alternative infection model for studying microbial infections. Unlike conventional animal models, invertebrate models are readily available and not restricted by ethical concerns. Husbandry, main...
is considered a suitable alternative infection model for studying microbial infections. Unlike conventional animal models, invertebrate models are readily available and not restricted by ethical concerns. Husbandry, maintenance, and handling of larvae are relatively simple. Furthermore, the insect innate immune system, consisting of a humoral and a cellular branch, shares similarities with the mammalian immune system. is a strictly human pathogen responsible for a range of clinical manifestations, from superficial uncomplicated infections to severe invasive diseases. Over the past decade, infection, serotype-specific virulence, and antimicrobial treatment have been studied using larvae. To further validate the infection model, this study investigated the -specific response of the larvae using a proteomics approach. Infected larvae responded by upregulation of recognition molecules, antimicrobial peptides, and general stress pathways and by activation of the phenol oxidase pathway. In addition, factors known to be involved in the inflammatory response in humans were upregulated, including 15-hydroxyprostaglandin dehydrogenase, macrophage migration inhibitory factor, and nucleobindin-2. In particular, the levels of C-type lectin receptors and C4b-binding protein alpha were elevated. In humans and mice, these proteins are known to interact directly with during the course of infection. Taken together, these results support the suitability of the model for studying infection to reduce the use of vertebrate model organisms.
mmu_circ_0012122/mmu-miR-1843-5p/Sertad2 axis: A novel regulatory pathway in rabies virus infection.
Ye Q, Tang X, Cai H … +6 more , Yuan M, Ba X, Tian Y, Chen J, Wang X, Xiang R
Virulence · 2026 Dec · PMID 42308359 · Full text
Rabies virus (RABV) causes severe central nervous system damage, though the underlying mechanisms remain unclear. Circular RNAs (circRNAs) have been identified in various cells and tissues and are known to regulate gene...
Rabies virus (RABV) causes severe central nervous system damage, though the underlying mechanisms remain unclear. Circular RNAs (circRNAs) have been identified in various cells and tissues and are known to regulate gene expression in eukaryotes. Here, we investigated the expression patterns of circRNAs in brain tissues from mice infected with two strains of RABV (CVS-11 and SRV9) and compared them to brain tissues from uninfected mice. Differential expression analysis identified 1,306 circRNAs, primarily derived from coding exons, with functional enrichment implicating synaptic and nervous system pathways. Critically, we identified and validated a novel regulatory axis, mmu_circ_0012122/mmu-miR-1843-5p/Sertad2, where mmu_circ_0012122 acts as a sponge for mmu-miR-1843-5p, leading to Sertad2 upregulation. This axis differentially modulated murine nerve cell fate: mmu_circ_0012122 knockdown reduced necrotic and non-viable apoptotic cells, while mmu-miR-1843-5p overexpression suppressed viable apoptosis and necrosis. Comprehensive characterization further identified Sertad2 as a key mediator promoting both nerve cell apoptosis and neuroinflammatory responses during infection. These findings underscored circRNAs as critical regulators of neuronal survival during RABV infection and highlighted the mmu_circ_0012122-driven network as a potential therapeutic target.
Integrative transcriptomic analysis uncovers the microRNA-centric regulation of Japanese encephalitis virus infection in porcine trophoblast cells.
Yang J, Jiang J, Gong J … +8 more , Zhang L, Li C, Bao X, Fan H, Dai C, Li Y, Chen S, Sun MA
Virulence · 2026 Dec · PMID 42308357 · Full text
Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic virus with pig as its major amplifying host. Despite that JEV can persistently infect the placentae of pregnant sows and cause severe reproductive failures,...
Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic virus with pig as its major amplifying host. Despite that JEV can persistently infect the placentae of pregnant sows and cause severe reproductive failures, the molecular responses and potential regulators of JEV infection in pig placenta remain unclear. Using porcine trophectoderm (pTr) cells as model, we investigated the transcriptomic changes during JEV infection, with a special focus on microRNA-centric regulation over immune genes and JEV infection. To avoid currently poor microRNA annotation for pig, we first performed small RNA-seq to achieve refined microRNA annotation, with hundreds of novel microRNAs annotated. After confirming that JEV can efficiently infect pTr cells and induce severe cytopathic effects, we conducted routine and small RNA-seq to determine the changes of mRNA and microRNA genes during JEV infection. We identified >1000 differentially expressed genes and found JEV-induced genes are tightly associated with antiviral immune responses. Moreover, we identified 94 JEV-affected microRNAs, including many with their roles on viral infection still unclear. Focusing on JEV-affected microRNAs, we constructed a microRNA-mRNA negative regulatory network, with multiple hub microRNAs and their targets inspected. Among these microRNAs, we experimentally validated that ssc-miR-149 and ssc-miR-483 both can inhibit JEV replication in pTr cells, with the well-recognized immune suppressor SOCS1 validated as a direct target of ssc-miR-149. Overall, this study comprehensively characterized the microRNA-centric regulation of JEV infection in pTr cells, which provides mechanistical insights into JEV infection in pig placenta and will facilitate the development of novel therapies against JEV infection.
Targeting metabolism and membrane: Neferine synergizes with gentamicin against by disrupting FNR/ArcA-Mediated homeostasis.
Yan Y, Zhao M, Zhao H … +3 more , Yan X, Kong L, Ma H
Virulence · 2026 Jun · PMID 42308356 · Publisher ↗
The escalating prevalence of antimicrobial-resistant bacteria, particularly in food and environmental settings, poses a severe global health threat. with rising resistance to gentamicin exemplifies this crisis, necessit...
The escalating prevalence of antimicrobial-resistant bacteria, particularly in food and environmental settings, poses a severe global health threat. with rising resistance to gentamicin exemplifies this crisis, necessitating novel strategies to restore antibiotic efficacy. This study identified Neferine, a bisbenzylisoquinoline alkaloid from Nelumbo nucifera, as a potent synergistic adjuvant for gentamicin against . Integrating high-throughput screening with bioinformatic and molecular biological approaches, we systematically investigated its synergistic efficacy and underlying mechanism.Our results demonstrated that Neferine, while lacking intrinsic bactericidal activity, dramatically enhanced gentamicin's potency, reducing its MIC by ≥16-fold, accelerating bactericidal kinetics, and delaying resistance development in vitro. Mechanistically, Neferine specifically targeted the global transcriptional regulators FNR and ArcA with high affinity (K_D = 1.3 μM and 658.6 nM, respectively), inducing conformational changes and disrupting their regulatory networks. This interaction hyper-activated the TCA cycle, leading to NAD /NADH imbalance, severe ATP depletion, and ROS burst, ultimately causing metabolic catastrophe. Concurrently, Neferine synergized with gentamicin to severely disrupt bacterial membrane integrity, increasing fluidity and provoking rapid depolarization. In vivo validation demonstrated that the combination significantly enhanced host survival, reduced bacterial loads in organs, and attenuated excessive inflammatory responses.In conclusion, Neferine synergizes with gentamicin through a dual mechanism: targeting FNR/ArcA to induce metabolic collapse and co-disrupting membrane integrity, offering a promising therapeutic strategy to combat multidrug-resistant infections.
The IL-17A/Neutrophil axis plays a critical role in lethal infection induced by an emerging ultra-virulent serotype 5 strain.
Chen G, Zhang X, Wang J … +4 more , Du P, Sun H, Zheng H, Xu J
Virulence · 2026 Dec · PMID 42308351 · Full text
() is an important emerging zoonotic pathogen. In recent years, ultra-virulent serotype 5 clinical strains have emerged in China, characterized by causing high mortality in mice at early infection, even at low inoculatio...
() is an important emerging zoonotic pathogen. In recent years, ultra-virulent serotype 5 clinical strains have emerged in China, characterized by causing high mortality in mice at early infection, even at low inoculation doses. In this study, we investigated the characteristics of lethal infection induced by the ultra-virulent serotype 5 strain SC2022MYS167 isolated from a patient with Streptococcal toxic shock-like syndrome (STSLS) and severe pneumonia. The lethal infection was associated with excessive bacterial loads and pro-inflammatory cytokines in peripheral blood and organs. Blocking IL-17A activity effectively reduced mouse mortality at infection stages 1 and 2. The lung tissues exhibited significantly higher levels of pro-inflammatory cytokines compared to liver and spleen tissues, with elevated IL-17A levels observed exclusively in the lung tissues of moribund mice at infection stage 1. CD11b Ly6G neutrophils recruited from peripheral blood significantly colocalized with IL-17A within lung tissues. Post-infection depletion of neutrophils rescued mice from lethal infection by significantly reducing the bacterial burden and levels of IL-17A, IL-6, and TNF-α in peripheral blood. A dose-dependent relationship was observed between neutrophil-depleting antibody and protection from lethal infection. These findings indicate the critical role of the IL-17A - neutrophil axis in STSLS development, pulmonary inflammation, pathological lesions, and subsequent acute host death induced by ultra-virulent serotype 5 strains, thereby providing a promising therapeutic target for reducing patient mortality.
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