生物学最新文献

{"title":"Involvement of oxidative stress in post-acute sequelae of COVID-19: clinical implications.","authors":"Paola Mayara Valente Coronel, Denise Caroline Luiz Soares Basilio, Isabelly Teixeira Espinoça, Kamylla Fernanda Souza de Souza, Nathalia Miranda Campos, Rafael Seiji Nakano Ota, Edgar Julian Paredes-Gamero, Danilo Wilhelm Filho, Ana Rita Coimbra Motta-Castro, Renata Trentin Perdomo, Eduardo Benedetti Parisotto","doi":"10.1080/13510002.2025.2471738","DOIUrl":"10.1080/13510002.2025.2471738","url":null,"abstract":"<p><p>Oxidative stress (OS) plays a key role in the pathophysiology of COVID-19 and may be associated with sequelae after severe SARS-CoV-2 infection. This study evaluated OS and inflammation biomarkers in blood from individuals with post-acute sequelae of COVID-19 (PASC). 64 male and female participants were distributed into three groups: healthy individuals (<i>n</i> = 20), acute COVID-19 patients (symptoms for <3 weeks, <i>n</i> = 15), and PASC patients (symptoms for >12 weeks, <i>n</i> = 29). Analyses included inflammatory cytokines, myeloperoxidase (MPO) activity, and OS markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione <i>S</i>-transferase (GST), gamma-glutamyl transferase (GGT), reduced glutathione (GSH), uric acid (UA), thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC). Individuals with PASC showed increased IL-6 and IL-8. Both COVID-19 groups exhibited decreased SOD and CAT. GST decreased only in the acute group. Elevated GGT and GSH were found in the PASC group. High UA levels were observed in PASC individuals. There were no changes in TBARS values ⁣⁣in the PASC group. However, PC concentrations were elevated only in this group. Correlations were identified between inflammatory markers and OS parameters. These findings suggest that individuals with PASC pronounced OS, which potentially exacerbates disease complications. Monitoring OS biomarkers could aid in patient prognosis and management.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2471738"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remimazolam induced cytotoxicity mediated through multiple stress pathways and acted synergistically with tyrosine kinase inhibitors in hepatocellular carcinoma.","authors":"Hsiu-Lung Fan, Jia-Lin Chen, Shu-Ting Liu, Jia-Tong Lee, Shih-Ming Huang, Zhi-Fu Wu, Hou-Chuan Lai","doi":"10.1080/13510002.2025.2475696","DOIUrl":"10.1080/13510002.2025.2475696","url":null,"abstract":"<p><p>The primary treatment for hepatocellular carcinoma (HCC) involves surgical removal of the primary tumor, but this creates a favorable environment for the proliferation and spread of residual and circulating cancer cells. The development of remimazolam-based balanced anesthesia is crucial for future antitumor applications. It is important to understand the mechanisms of cytotoxicity for HCC in detail.</p><p><p>We performed cell viability analysis, western blotting analysis, reverse transcription-polymerase chain reaction analysis, and flow cytometry analysis in two HCC cell lines, HepG2 and Hep3B cells.</p><p><p>Our data demonstrated that remimazolam induced cytotoxicity by suppressing cell proliferation, inhibiting G1 phase progression, and affecting mitochondrial reactive oxygen species (ROS) levels, leading to apoptosis, DNA damage, cytosolic ROS elevation, lipid peroxidation, autophagy, mitochondrial depolarization, and endoplasmic reticulum stress. Inhibitors of apoptosis, autophagic cell death, and ferroptosis and a ROS scavenger failed to rescue cell death caused by remimazolam besylate. Our combination index revealed that remimazolam besylate has the potential to act as a sensitizer for targeted tyrosine kinase inhibitor therapy for HCC.</p><p><p>Our findings open up new possibilities for combinatory HCC therapy using remimazolam, leveraging its dual functional roles in surgery and drug therapy for liver cancers.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2475696"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prp16 enables efficient splicing of introns with diverse exonic consensus elements in the short-intron rich <i>Cryptococcus neoformans</i> transcriptome.","authors":"Manendra Singh Negi, Vishnu Priya Krishnan, Niharika Saraf, Usha Vijayraghavan","doi":"10.1080/15476286.2025.2477844","DOIUrl":"10.1080/15476286.2025.2477844","url":null,"abstract":"<p><p>DEAH box splicing helicase Prp16 in budding yeast governs spliceosomal remodelling from the branching conformation (C complex) to the exon ligation conformation (C* complex). In this study, we examined the genome-wide functions of Prp16 in the short intron-rich genome of the basidiomycete yeast <i>Cryptococcus neoformans</i>. The presence of multiple introns per transcript with intronic features that are more similar to those of higher eukaryotes makes it a promising model for studying spliceosomal splicing. Using a promoter-shutdown conditional Prp16 knockdown strain, we uncovered genome-wide but substrate-specific roles in <i>C. neoformans</i> splicing. The splicing functions of Prp16 are dependent on helicase motifs I and II, which are conserved motifs for helicase activity. A small subset of introns spliced independent of Prp16 activity was investigated to discover that exonic sequences at the 5' splice site (5'SS) and 3' splice site (3'SS) with stronger affinity for U5 loop 1 are a common feature in these introns. Furthermore, short (60-100nts) and ultrashort introns (<60nts) prevalent in the <i>C. neoformans</i> transcriptome were more sensitive to Prp16 knockdown than longer introns, indicating that Prp16 is required for the efficient splicing of short and ultrashort introns. We propose that stronger U5 snRNA-pre-mRNA interactions enable efficient transition of the spliceosome from the first to the second catalytic confirmation in Prp16 knockdown, particularly for short introns and introns with suboptimal features. This study provides insights into fine-tuning spliceosomal helicase function with variations in <i>cis-</i>element features.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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":"Synergistic effects of AgNPs and zileuton on PCOS via ferroptosis and inflammation mitigation.","authors":"Amira K Eltokhy, Rehab Ahmed Ahmed El-Shaer, Omnia Safwat El-Deeb, Eman E Farghal, Rowida Raafat Ibrahim, Rasha Elesawy, Marwa Mahmoud Awad, Radwa Ismail, Shaimaa M Motawea, Doaa Shatat, Yasser Mostafa Hafez, Hend Ahmed El Hanafy, Marwa Mohamed Atef","doi":"10.1080/13510002.2024.2445398","DOIUrl":"https://doi.org/10.1080/13510002.2024.2445398","url":null,"abstract":"<p><strong>Background: </strong>The most prevalent endocrine disorder affecting women is PCOS. Programmed death of ovarian cells has yet to be elucidated. Ferroptosis is a kind of iron-dependent necrosis featured by significantly Fe⁺²-dependent lipid peroxidation. The ongoing study aimed to reinforce fertility by combining therapy with AgNPs and (Zileuton) in PCOS rats' model.</p><p><strong>Methods: </strong>The study included 75 adult female rats divided into 5 groups; control, PCOS, PCOS treated with AgNPs, PCOS treated with Zileuton, and PCOS group treated with AgNPs and Zileuton. The study investigated the anti-ferroptotic, anti-inflammatory, antioxidant, antiapoptotic, histopathological and immunohistochemical examinations of COX-2 and VEGF.</p><p><strong>Results: </strong>The combination of AgNPs and Zileuton showed significant reduction of inflammatory mediators (IL-6, TNF-α, NFk-B) compared with diseased group (<i>P</i>-<i>value</i> < 0.05), regression of ferroptosis marks (Panx1 and TLR4 expression, Fe⁺² levels) compared with diseased group (<i>P</i>-<i>value</i> < 0.05), depression of apoptotic marker caspase 3 level compared with diseased animals (<i>P</i>-value < 0.05), depression of MDA level, elevation of HO-1, GPx4 activity, and reduction of Cox2 and VEGF as compared with the diseased, AgNPs or zileuton-treated groups (<i>P</i>-value < 0.05).</p><p><strong>Conclusion: </strong>The study showed that the combination of AgNPs and zileuton guards against, inflammation, apoptosis, and ferroptosis in PCO.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2445398"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the versatility of <i>Drosophila melanogaster</i> as a model organism in biomedical research: a comprehensive review.","authors":"Ayomide Victor Atoki, Patrick Maduabuchi Aja, Tijjani Salihu Shinkafi, Erick Nyakundi Ondari, Adekunle Ismahil Adeniyi, Ilemobayo Victor Fasogbon, Reuben Samson Dangana, Umar Uthman Shehu, Akinpelumi Akin-Adewumi","doi":"10.1080/19336934.2024.2420453","DOIUrl":"https://doi.org/10.1080/19336934.2024.2420453","url":null,"abstract":"<p><p><i>Drosophila melanogaster</i> is a highly versatile model organism that has profoundly advanced our understanding of human diseases. With more than 60% of its genes having human homologs, <i>Drosophila</i> provides an invaluable system for modelling a wide range of pathologies, including neurodegenerative disorders, cancer, metabolic diseases, as well as cardiac and muscular conditions. This review highlights key developments in utilizing <i>Drosophila</i> for disease modelling, emphasizing the genetic tools that have transformed research in this field. Technologies such as the GAL4/UAS system, RNA interference (RNAi) and CRISPR-Cas9 have enabled precise genetic manipulation, with CRISPR-Cas9 allowing for the introduction of human disease mutations into orthologous <i>Drosophila</i> genes. These approaches have yielded critical insights into disease mechanisms, identified novel therapeutic targets and facilitated both drug screening and toxicological studies. Articles were selected based on their relevance, impact and contribution to the field, with a particular focus on studies offering innovative perspectives on disease mechanisms or therapeutic strategies. Our findings emphasize the central role of <i>Drosophila</i> in studying complex human diseases, underscoring its genetic similarities to humans and its effectiveness in modelling conditions such as Alzheimer's disease, Parkinson's disease and cancer. This review reaffirms <i>Drosophila</i>'s critical role as a model organism, highlighting its potential to drive future research and therapeutic advancements.</p>","PeriodicalId":12128,"journal":{"name":"Fly","volume":"19 1","pages":"2420453"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","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":"Epigenome-wide association study of perceived discrimination in the Multi-Ethnic Study of Atherosclerosis (MESA).","authors":"Wei Zhao, Lisha Lin, Kristen M Kelly, Lauren A Opsasnick, Belinda L Needham, Yongmei Liu, Srijan Sen, Jennifer A Smith","doi":"10.1080/15592294.2024.2445447","DOIUrl":"https://doi.org/10.1080/15592294.2024.2445447","url":null,"abstract":"<p><p>Perceived discrimination, recognized as a chronic psychosocial stressor, has adverse consequences on health. DNA methylation (DNAm) may be a potential mechanism by which stressors get embedded into the human body at the molecular level and subsequently affect health outcomes. However, relatively little is known about the effects of perceived discrimination on DNAm. To identify the DNAm sites across the epigenome that are associated with discrimination, we conducted epigenome-wide association analyses (EWAS) of three discrimination measures (everyday discrimination, race-related major discrimination, and non-race-related major discrimination) in 1,151 participants, including 565 non-Hispanic White, 221 African American, and 365 Hispanic individuals, from the Multi-Ethnic Study of Atherosclerosis (MESA). We conducted both race/ethnicity-stratified analyses as well as trans-ancestry meta-analyses. At false discovery rate of 10%, 7 CpGs and 4 differentially methylated regions (DMRs) containing 11 CpGs were associated with perceived discrimination exposures in at least one racial/ethnic group or in meta-analysis. Identified CpGs and/or nearby genes have been implicated in cellular development pathways, transcription factor binding, cancer and multiple autoimmune and/or inflammatory diseases. Of the identified CpGs (7 individual CpGs and 11 within DMRs), two CpGs and one CpG within a DMR were associated with expression of cis genes <i>NDUFS5</i>, <i>AK1RIN1</i>, <i>NCF4</i> and <i>ADSSL1</i>. Our study demonstrated the potential influence of discrimination on DNAm and subsequent gene expression.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2445447"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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}