Virulence最新文献

{"title":"Guanosine enhances the bactericidal effect of ceftiofur sodium on <i>Streptococcus suis</i> by activating bacterial metabolism.","authors":"Yue Dong, Xiaona Liu, Shanshan Xiong, Mingyu Cao, Haojie Wu, Long Chen, Mengmeng Zhao, Yadan Zheng, Zhiyun Zhang, Yanyan Liu, Yanhua Li, Qianwei Qu, Chunliu Dong","doi":"10.1080/21505594.2025.2453525","DOIUrl":"10.1080/21505594.2025.2453525","url":null,"abstract":"<p><p>The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. <i>Streptococcus suis</i> (<i>S. suis</i>) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant <i>S. suis</i>. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) <i>in vitro</i> and <i>in vivo</i>. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of <i>S. suis</i> infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2453525"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between HERVs and exogenous viral infections: A focus on the value of HERVs in disease prediction and treatment.","authors":"Anhua Dou, Juan Xu, Chenglin Zhou","doi":"10.1080/21505594.2025.2523888","DOIUrl":"https://doi.org/10.1080/21505594.2025.2523888","url":null,"abstract":"<p><p>Human endogenous retroviruses (HERVs) are virus-related sequences that are a normal part of the human genome; they account for about 8% of the human genome. Reactivation of these ancestral proviral sequences can lead to the generation of functional products. Several reactivated HERVs are associated with cancer and autoimmune diseases. Emerging research suggests that reactivated HERVs may play a significant role in the development of viral diseases such as acquired immune deficiency syndrome (AIDS) and coronavirus disease 2019 (COVID-19), as well as in neuroinflammatory diseases possibly triggered by viral factors, such as multiple sclerosis (MS). Studies exploring the relationship between HERVs and exogenous viral infections have the potential to offer a fresh perspective on developing treatment and prevention strategies for exogenous viral infections. The mechanism of the transactivation of HERVs caused by exogenous viral infection, as well as the contribution of HERVs to viral diseases or diseases triggered by viral factors, deserve further research. Here, we review the relationship between exogenous viruses and HERVs in several common diseases caused or triggered by viral infections, with a focus on the value of HERVs as biomarkers for forecasting disease advancement or prognosis and as potential targets for therapeutic interventions.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2523888"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PA-X host shutoff site 100 V exerts a contrary effect on viral fitness of the highly pathogenic H7N9 influenza A virus in mice and chickens.","authors":"Xia Chen, Ming Kong, Chunxi Ma, Manyu Zhang, Zenglei Hu, Min Gu, Xiaoquan Wang, Ruyi Gao, Shunlin Hu, Yu Chen, Xiaowen Liu, Daxin Peng, Xiufan Liu, Jiao Hu","doi":"10.1080/21505594.2024.2445238","DOIUrl":"https://doi.org/10.1080/21505594.2024.2445238","url":null,"abstract":"<p><p>Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed \"host shutoff.\" Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery. IAV PA-X is one of these factors that selectively shuts off the global host genes. However, the specific role of PA-X host shutoff activity in viral fitness of IAV remains poorly understood. Herein, we successfully mapped PA-X 100 V as a novel site important for host shutoff of the H7N9 and H5N1 viruses. By analysing the polymorphism of this residue in various subtype viruses, we found that PA-X 100 was highly variable in H7N9 viruses. Structural analysis revealed that 100 V was generally close to the PA-X endonuclease active site, which may account for its host shutoff activity. By generating the corresponding mutant viruses derived from the parental H7N9 virus and the PA-X-deficient H7N9 virus, we determined that PA-X 100 V significantly enhanced viral fitness in mice while diminishing viral virulence in chickens. Mechanistically, PA-X 100 V significantly increased viral polymerase activity and viral replication in mammalian cells. Furthermore, PA-X 100 V highly blunted the global host response in 293T cells, particularly restraining genes involved in energy metabolism and inflammatory response. Collectively, our data provided information about the intricate role of the PA-X host shutoff site in regulating the viral fitness of the H7N9 influenza virus, which furthers our understanding of the complicated pathogenesis of the influenza A virus.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2445238"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Klebsiella pneumoniae</i> derived outer membrane vesicles mediated bacterial virulence, antibiotic resistance, host immune responses and clinical applications.","authors":"Lifeng Li, Xinxiu Xu, Ping Cheng, Zengyuan Yu, Mingchao Li, Zhidan Yu, Weyland Cheng, Wancun Zhang, Huiqing Sun, Xiaorui Song","doi":"10.1080/21505594.2025.2449722","DOIUrl":"10.1080/21505594.2025.2449722","url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> is a gram-negative pathogen that can cause multiple diseases including sepsis, urinary tract infections, and pneumonia. The escalating detections of hypervirulent and antibiotic-resistant isolates are giving rise to growing public concerns. Outer membrane vesicles (OMVs) are spherical vesicles containing bioactive substances including lipopolysaccharides, peptidoglycans, periplasmic and cytoplasmic proteins, and nucleic acids. Emerging studies have reported various roles of OMVs in bacterial virulence, antibiotic resistance, stress adaptation, and host interactions, whereas knowledge on their roles in <i>K. pneumoniae</i> is currently unclear. In this review, we summarized recent progress on the biogenesis, components, and biological function of <i>K. pneumoniae</i> OMVs, the impact and action mechanism in virulence, antibiotic resistance, and host immune response. We also deliberated on the potential of <i>K. pneumoniae</i> OMVs in vaccine development, as diagnostic biomarkers, and as drug nanocarriers. In conclusion, <i>K. pneumoniae</i> OMVs hold great promise in the prevention and control of infectious diseases, which merits further investigation.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2449722"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and vaccine efficacy of <i>Actinobacillus pleuropneumoniae</i>-derived extracellular vesicles as a novel vaccine candidate.","authors":"Su Hyun Park, Yun Hye Kim, Hyeon Jin Lee, Jeong Moo Han, Byoung-Joo Seo, Gyeong-Seo Park, Chonghan Kim, Young Bae Ryu, Woo Sik Kim","doi":"10.1080/21505594.2025.2453818","DOIUrl":"10.1080/21505594.2025.2453818","url":null,"abstract":"<p><p><i>Actinobacillus pleuropneumoniae</i> (APP) is a significant pathogen in the swine industry, leading to substantial economic losses and highlighting the need for effective vaccines. This study evaluates the potential of APP-derived extracellular vesicles (APP-EVs) as a vaccine candidate compared to the commercial Coglapix vaccine. APP-EVs, isolated using tangential flow filtration (TFF) and cushioned ultracentrifugation, exhibited an average size of 105 nm and a zeta potential of -17.4 mV. These EVs demonstrated stability under external stressors, such as pH changes and enzymatic exposure and were found to contain 86 major metabolites. Additionally, APP-EVs induced dendritic cell (DC) maturation in a Toll-like receptor 4 (TLR4)-dependent manner without cytotoxicity. APP-EVs predominantly elicited Th1-mediated IgG responses in immunized mice without significant liver and kidney toxicity. Contrarily, unlike Coglapix, which induced stronger Th2-mediated responses and notable toxicity. In addition, APP-EVs triggered APP-specific Th1, Th17, and cytotoxic T lymphocyte (CTL) responses and promoted the activation of multifunctional T-cells. Notably, APP-EV immunization enhanced macrophage phagocytosis and improved survival rates in mice challenged with APP infection compared to those treated with Coglapix. These findings suggest that APP-EVs are promising vaccine candidates, capable of inducing potent APP-specific T-cell responses, particularly Th1, Th17, CTL, and multifunctional T-cells, thereby enhancing the protective immune response against APP infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2453818"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of glutathione for oxidative stress and pathogenicity of <i>Streptococcus suis</i>.","authors":"Wei Peng, Qinggen Jiang, Yuting Wu, Li He, Bei Li, Weicheng Bei, Xia Yang","doi":"10.1080/21505594.2025.2474866","DOIUrl":"10.1080/21505594.2025.2474866","url":null,"abstract":"<p><p><i>Streptococcus suis</i> is an important zoonotic pathogen that threatens human and pig health. During infection, the host can impose oxidative stress to resist pathogen invasion. Resistance to oxidative toxicity is an important factor for pathogens. Glutathione synthesis contributes to reactive oxygen species (ROS) detoxification in bacterial cells. Little is known about the roles of glutathione synthesis and transport in <i>S</i>. <i>suis</i>. In this study, we demonstrated that glutathione treatment increased oxidative stress tolerance in <i>S</i>. <i>suis</i>. GshAB and GshT were found in <i>S</i>. <i>suis</i> glutathione synthesis and import by bioinformatics. In vitro, inactivation of <i>gshAB</i> and <i>gshT</i> led to increased sensitivity to oxidative stress. Inactivation of <i>gshT</i> led to growth defects in the medium. The intracellular glutathione content of <i>gshAB</i> or <i>gshT</i> deletion mutants was lower than that of wild type (WT) strain. The phagocytic resistance of <i>gshAB</i> and <i>gshT</i> mutants was lower than that of the WT strain. Moreover, the virulence of <i>gshAB</i> and <i>gshT</i> deletion mutants was significantly lower than that of the WT strain in mouse survival and tissue loading experiments. In conclusion, these results revealed the functions of GshAB and GshT in the pathogenesis of <i>S. suis</i>. These findings enhance our understanding of bacterial virulence mechanisms and may provide a new avenue for therapeutic intervention aimed at curbing <i>S. suis</i> infections.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2474866"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alongshan virus: An emerging arboviral challenge in regional health security.","authors":"Meixi Ren, Zheng Pang, Yingxin Tu, Anan Wang, Tao Xu, Xiaoli Yu, Guoyu Niu","doi":"10.1080/21505594.2025.2492360","DOIUrl":"https://doi.org/10.1080/21505594.2025.2492360","url":null,"abstract":"<p><p>The Alongshan virus (ALSV), classified within the Flaviviridae family and belonging to the Jingmenvirus group, is a segmented RNA virus that was first identified in China in 2017. Since then, it has been reported in several Eurasian countries. Although no confirmed fatal cases have been documented, the potential public health risks associated with ALSV are significant and warrant serious attention. The emergence of ALSV has not only broadened the array of tick-borne diseases but has also enriched the research landscape surrounding segmented flaviviruses. Despite these advancements, our understanding of ALSV is still nascent, and its complex infection pathways remain largely unexplored. This review seeks to offer an in-depth examination of ALSV, addressing its biological properties, molecular features, epidemiological data, clinical presentations, and diagnostic methodologies. Our objective is to promote progress in the formulation of preventive, diagnostic, and therapeutic measures for this emerging segmented flavivirus.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2492360"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine cGAS-STING signalling induced apoptosis negatively regulates STING downstream IFN response and autophagy via different mechanisms.","authors":"Nengwen Xia, Anjing Liu, Hongjian Han, Sen Jiang, Qi Cao, Jia Luo, Jiajia Zhang, Weilin Hao, Ziyan Sun, Nanhua Chen, Huiling Zhang, Wanglong Zheng, Jianzhong Zhu","doi":"10.1080/21505594.2025.2496436","DOIUrl":"https://doi.org/10.1080/21505594.2025.2496436","url":null,"abstract":"<p><p>The innate immune cGAS-STING signalling pathway recognizes double-stranded DNA and induces the interferon (IFN) response, autophagy and apoptosis, exerting a broad antiviral effect. However, the mechanisms and interrelationship between STING induced downstream IFN, autophagy, and apoptosis in livestock have not been fully elucidated. Our previous study defined porcine STING (pSTING) induced IFN, autophagy and apoptosis, and showed that IFN does not affect autophagy and apoptosis, whereas autophagy inhibits both IFN and apoptosis, likely by promoting pSTING degradation. In this study, we further explored the underlying mechanism of pSTING induced apoptosis and the regulation of IFN and autophagy by apoptosis. First, pSTING induces endoplasmic reticulum (ER) stress and mitochondrial damage to activate caspases 9, 3, and 7, which drive intrinsic apoptosis. Second, pSTING triggered apoptosis inhibits the IFN response by activating caspase 7, which cleaves pIRF3 at the species specific D197/D198 site. Third, pSTING activated apoptotic caspases 9, 3, and 7 reduce the expression of ATG proteins, and cleave the ATG5-ATG12L1 complex, effectively inhibiting autophagy. Fourth, knockout of pSTING activated apoptosis heightens the IFN response and autophagy, while suppressing the replication of Herpes Simplex Virus type 1 (HSV-1), Vesicular Stomatitis Virus (VSV) and Pseudorabies Virus (PRV). This study sheds light on the molecular mechanisms of innate immunity in pigs.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2496436"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenacapavir's success: Revitalizing antiviral drug discovery.","authors":"Daniel Miranda, David Jesse Sanchez","doi":"10.1080/21505594.2025.2497902","DOIUrl":"https://doi.org/10.1080/21505594.2025.2497902","url":null,"abstract":"","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2497902"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Staphylococcus aureus nt5</i> gene mutation through CRISPR RNA-guided base editing weakens bacterial virulence and immune evasion.","authors":"Xinpeng Liu, Lan Huang, Yang Ye, Haiyi Wang, Min Tang, Fuqiang He, Zijing Xia, Shi Deng, Peng Zhang, Ruiwu Dai, Shufang Liang","doi":"10.1080/21505594.2025.2451163","DOIUrl":"10.1080/21505594.2025.2451163","url":null,"abstract":"<p><p>The resistance of commonly used clinical antibiotics, such as daptomycin (DAP), has become increasingly serious in the fight against <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infection. It is essential to explore key pathogenicity-driven genes/proteins in bacterial infection and antibiotics resistance, which contributes to develop novel therapeutic strategies against <i>S. aureus</i> infections. The <i>nt5</i> gene of <i>S. aureus</i>, encoding 5'-nucleotidase (NT5), is nearly unknown for its function in drug resistance and bacterial infection. Herein, to reveal <i>nt5</i> gene role in drug resistance and infection ability of <i>S. aureus</i>, we performed <i>nt5</i>^C166T gene mutation using a clustered regulatory interspaced short palindromic repeat ribonucleic acid (RNA)-guided base editing system to investigate the lose-of-function of NT5 protein. Subsequent transcriptome sequencing of the mutant strain revealed that <i>nt5</i> inactivation caused changes in cell membrane integrity and inhibited nucleotide metabolism, suggesting the <i>nt5</i> gene may be involved in bacterial drug resistance and virulence. The mutant strain exhibited enhanced tolerance to DAP treatment by attenuating cell membrane potential dissipation and slowing deoxyribonucleic acid release. Moreover, the <i>nt5</i> mutation alleviated abscess degree of mouse kidneys caused by <i>S. aureus</i> infection byreducing the expression of IL-1β, IL-6, and IL-18. The <i>nt5</i> mutant strain was easily swallowed by host immune cells, resulting in weak bacterial toxicity of the <i>S. aureus</i> mutant in the bacterial infection process. In summary, <i>nt5</i> gene mutation confers tolerance to DAP and a lower bacterial capacity to form kidney abscesses through phagocytosis of host immune cells, which indicates the targeted inhibition of NT5 protein would offer a potential new therapeutic strategy against <i>S. aureus</i> infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2451163"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}