Virulence最新文献

{"title":"Protein disulphide isomerase A4 as a potential biomarker for coronavirus disease 2019: Correlation with cytokine profiles and disease progression.","authors":"Yu-Hsiu Chang, Ying-Chuan Wang, Yun-Chen Liu, Chun-Hsiang Chiu","doi":"10.1080/21505594.2025.2508815","DOIUrl":"10.1080/21505594.2025.2508815","url":null,"abstract":"<p><p>This study investigated the role of protein disulphide isomerase A4 (PDIA4) in the pathogenesis of coronavirus disease 2019 (COVID-19), focusing on its relationship with disease severity and potential as a biomarker. We analysed a cohort of adult COVID-19 patients with varying disease severity, grouped by vaccination status. Serum levels of PDIA4 and cytokines (interleukin [IL]-6, interferon gamma inducible protein-10 [IP-10], IL-16, monocyte chemoattractant protein-1 [MCP-1], and platelet-derived growth factor-BB [PDGF-BB]) were measured using enzyme-linked immunosorbent assay and compared among patients with different disease severities. Statistical analyses were performed to assess the correlation between PDIA4 levels, disease severity, and inflammatory markers. Unvaccinated COVID-19 patients with pneumonia had significantly higher PDIA4 levels than those without pneumonia (517.94 ± 264 vs. 284.86 ± 2.24; <i>p</i> = 0.0022). Although unvaccinated patients requiring oxygen support exhibited higher PDIA4 levels than those not requiring oxygen (519.30 ± 269.67 vs. 420.89 ± 240.49; <i>p</i> = 0.4825), the difference was not statistically significant. No significant difference was observed in the PDIA4 levels between unvaccinated patients with and without respiratory failure. Levels of PDIA4 were positively correlated with the levels of IL-16, MCP-1, IP-10, and IL-6 (correlation coefficients: 0.28-0.62), although this correlation was weaker or absent in vaccinated patients. Our findings suggest that PDIA4 is associated with COVID-19 severity and may serve as a potential biomarker of disease progression. Further studies are needed to elucidate the mechanisms by which PDIA4 influences the immune response and assess its potential for therapeutic exploration in COVID-19.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2508815"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112215","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":"Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5.","authors":"Hankun Wang, Chunling Zhang, Moran Li, Wangchun Zhao, Jialin Wang, Yanhong Ran, Xiaoping Yang, Zemin Deng, Jun Chen, Hongjian Li","doi":"10.1080/21505594.2025.2500493","DOIUrl":"10.1080/21505594.2025.2500493","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) is a typical opportunistic human pathogen, which can endanger the lives of individuals with immune insufficiency or low immune function. One of the most effective immune mechanisms against HCMV in host cells is the production of antiviral cytokines. Chemokines are small secreted proteins produced by cell immune responses to inflammatory stimuli or viral infection and act as potent chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes, and thus play a significant role in antiviral defence. Viruses have also evolved multiple strategies to resist the host's immune system while coexisting with the host. In this study, based on RNA sequencing transcriptome differential analysis, we found that HCMV encoded UL23 May specifically down-regulate chemokines Chemokine ligand 2 (CCL2) and Chemokine ligand 5 (CCL5). Next, we determined that UL23 could inhibit the expression of Chemokine CCL2 and CCL5 by mainly affecting the phosphorylation of IRF-3, and then inhibited the migration of immune cells and blocked the antiviral immune responses in the migration and co-culture assays of HCMV-infected cells with immune migration-related cells. In conclusion, these results highlight that UL23 plays an important role in the immune evasion of HCMV by specially inhibiting the expression of chemokines CCL2 and CCL5, impairing the recruitment of immune cells by infected host cells and helping the virus escape immune killing.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2500493"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302978","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>Streptococcus suis</i> serotype 5: Emerging zoonotic threat with distinct genomic heterogeneity.","authors":"Xiyan Zhang, Jinlu Zhu, Anusak Kerdsin, Jianping Wang, Mingliu Wang, Hui Yang, Weiming Kang, Xiaojing Lu, Yan Wang, Hui Sun, Marcelo Gottschalk, Han Zheng, Jianguo Xu, Zongfu Wu","doi":"10.1080/21505594.2025.2523882","DOIUrl":"https://doi.org/10.1080/21505594.2025.2523882","url":null,"abstract":"<p><p><i>Streptococcus suis</i> is a significant pig pathogen and an emerging zoonotic agent. Serotype 5 is becoming an increasing concern among pigs and humans with <i>S. suis</i> infection worldwide. This study investigated the population structure, phylogenetic relationship, genomic characteristics, and virulence of serotype 5 population, analyzing 89 isolates, including eight from human cases. The results revealed significant genomic heterogeneity and diverse virulence levels within serotype 5 population. Phylogenetic analysis identified two distinct lineages with notable differences in evolution and genomic traits. Thirty-two representative serotype 5 strains were clustered into four groups: ultra-highly virulent (UV) (<i>n</i> = 1), highly virulent plus (HV⁺) (<i>n</i> = 4), HV (<i>n</i> = 11), and virulent (V) (<i>n</i> = 16). Virulence levels progressively decreased from the UV group to HV⁺, HV, and V groups. The UV, HV⁺, and HV strains induced significantly lethal infection in mice during the early phase of infection. The lethal infection induced by UV and HV⁺ strains was time-dependent but dose-independent. Ultra-high bacterial loads, excessive pro-inflammatory cytokines, and severe organ damage were responsible for the sudden death of mice infected with UV strain at the early phase of infection. The capacity to establish infection, induce excessive pro-inflammatory cytokine production, and elevate biomarkers associated with organ damage varied significantly among HV⁺ strains. The V strains demonstrated the capacity to induce delayed lethal infection. These findings emphasized the serious public health risk posed by serotype 5 strains. The valuable information for developing effective prevention and control strategies for <i>S. suis</i> serotype 5 infections was provided.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2523882"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508613","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":"Multi-omics profiling of acute <i>Pseudomonas aeruginosa</i> pneumonia unmasks conventional NK cell depletion and stage-specific therapeutic targets.","authors":"Fuliang Zong, Nan Xiao, Yifeng Wang, Duo Su, Dongsheng Zhou, Lingfei Hu, Huiying Yang","doi":"10.1080/21505594.2025.2490206","DOIUrl":"https://doi.org/10.1080/21505594.2025.2490206","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> (PA) is a key pathogen in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), challenging clinical medicine. This study aims to elucidate the characteristics of the host's innate immune response following inhalational PA infection. We developed a mouse model by aerosolized intratracheal inoculation with PA and conducted a comprehensive analysis at the protein, cellular, and gene expression levels. Protein analysis revealed a substantial increase in inflammatory proteins in the bronchoalveolar lavage fluid and serum, indicating a robust inflammatory response in the lungs and systemic circulation. Cellular investigations showed an increase in neutrophils, monocytes, and alveolar macrophages during infection, whereas NK cells showed a marked reduction from 5.88% pre-infection to 2.41% at 24 h (<i>p</i> = 0.0102) and 1.55% by 48 h (<i>p</i> = 0.0023). To assess gene expression changes, RNA-sequencing technology was employed to map the temporal shifts in the transcriptional profile of the host lung post-infection. We analysed the expression patterns and dynamic transcriptional characteristics of differentially expressed genes (DEGs), describing the inflammation progression. Importantly, Through the analysis of single-cell RNA sequencing (scRNA-seq) datasets in public repositories, we observed the reduction in conventional natural killer (cNK) cells, rather than tissue-resident natural killer (trNK) cells in the early stages of PA infection. Sequential scRNA-seq analysis resolved NK-subset heterogeneity, revealing that cNK dominance (77.8% of total NK cells) under homeostasis collapsed to 9.2% within 24 h post-infection. Our findings establish cNK attrition as the earliest immune checkpoint failure in PA pneumonia and provide proof-of-concept for cNK-targeted immunotherapies to counteract lethal pulmonary infections. Keywords: <i>Pseudomonas aeruginosa</i>, aerosolized intratracheal inoculation, conventional NK cells, innate immunity, RNA-sequencing.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2490206"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021655","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>UvCYP503</i> is required for stress response and pathogenicity in <i>Ustilaginoidea virens</i>.","authors":"Xiuxiu Cao, Hui Wen, Dagang Tian, Huanbin Shi, Kabin Xie, Jiehua Qiu, Yanjun Kou","doi":"10.1080/21505594.2025.2472877","DOIUrl":"10.1080/21505594.2025.2472877","url":null,"abstract":"<p><p>The fungus <i>Ustilaginoidea virens</i>, which impacts rice spikes, causes rice false smut (RFS), a significant prevalent disease in rice cultivation regions globally. Cytochrome <i>P450</i> genes are known to be involved in secondary metabolism and pathogenesis in various species, but studies on <i>CYP450</i> genes in <i>U. virens</i> are limited. In this research, a <i>P450</i> family gene, <i>CYP503</i>, was found up-regulated during invasion stage of <i>U. virens</i>. Observation of fluorescence indicated that UvCYP503-GFP is situated within cytoplasm of hyphae. Disruption of <i>CYP503</i> led to decreased hyphal development, conidiation, and pathogenicity. Additional RNA-seq assay revealed that <i>UvCYP503</i> affects the transcript of genes associated with pathogenicity, various stress responses, and other <i>CYP450</i> genes. In alignment with RNA-seq results, compared with wild-type, Δ<i>Uvcyp503</i> mutants showed increased sensitivity to cell wall stresses, but reduced sensitivity to osmotic and hyperosmotic stressors. Moreover, Δ<i>Uvcyp503</i> mutants exhibited decreased sensitivity to the fungicides difenoconazole and tebuconazole. This study represents a phenome-based functional analysis of a <i>CYP503</i> gene in <i>U. virens</i> and provides valuable genetic resources for further research in filamentous fungi and other plant pathogens.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2472877"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543726","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":"Assessment for antibiotic resistance in <i>Helicobacter pylori</i>: A practical and interpretable machine learning model based on genome-wide genetic variation.","authors":"Yingying Wang, Shuwen Zheng, Rui Guo, Yanke Li, Honghao Yin, Xunan Qiu, Jijun Chen, Chuxuan Ni, Yuan Yuan, Yuehua Gong","doi":"10.1080/21505594.2025.2481503","DOIUrl":"10.1080/21505594.2025.2481503","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) antibiotic resistance poses a global health threat. Accurate identification of antibiotic resistant strains is essential for the control of infection. In the present study, our goal is to leverage the whole-genome data of <i>H. pylori</i> to develop practical and interpretable machine learning (ML) models for comprehensive antibiotic resistance assessment. A total of 296 <i>H. pylori</i> isolates with genome-wide data were downloaded from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) and the National Center for Biotechnology Information (NCBI) databases. By training ML models on feature sets of single nucleotide polymorphisms from SNP calling (SNPs-1), antibiotic-resistance SNP annotated by the Comprehensive Antibiotic Resistance Database (SNPs-2), gene presence or absence (GPA), we generated predictive models for four antibiotics and multidrug-resistance (MDR). Among them, the models that combined SNPs-1, SNPs-2, and GPA data demonstrated the best performance, with the eXtreme Gradient Boosting (XGBoost) consistently outperforming others. And then we utilized the SHapley Additive exPlanations (SHAP) method to interpret the ML models. Furthermore, a free web application for the MDR model was deployed to the GitHub repository (https://H.pylori/MDR/App/). Our study demonstrated the promise of employing whole-genome data in conjunction with ML algorithms to forecast <i>H. pylori</i> antibiotic resistance. In the future, the application of this approach for predicting <i>H. pylori</i> antibiotic resistance would hold the potential to mitigate the empiric administration.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2481503"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677337","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":"Chemosensory protein 16 has an immune function and participates in host-pathogen interaction in <i>Galleria mellonella</i> infected with <i>Pseudomonas entomophila</i>.","authors":"Jakub Kordaczuk, Michał Sułek, Paweł Mak, Alicja Frączek, Iwona Wojda","doi":"10.1080/21505594.2025.2471367","DOIUrl":"10.1080/21505594.2025.2471367","url":null,"abstract":"<p><p>Chemosensory protein 16 was identified in the hemolymph of <i>Galleria mellonella</i> as a protein with an amount increasing after oral infection with 10^3 CFU of <i>Pseudomonas entomophila</i>, and decreasing after infection with a higher dose (10^5 CFU) of bacteria. The expression of the CSP16 gene occurred in the fat body and in the gut and correlated with changes in the protein level in the hemolymph. The CSP16 protein inhibited <i>P. entomophila</i> growth in the concentration range from 0.15 to 6 nM. Additionally, the CSP16 protein showed bactericidal activity against <i>P. entomophila, Bacillus thuringiensis</i>, and <i>Escherichia coli</i> in the range of 2-18 μM, but only in the presence of protease inhibitors, otherwise it was degraded by extracellular proteases secreted by <i>P. entomophila</i>. We demonstrated that the bactericidal activity of CSP16 was related to its ability to perforate bacterial cellular membranes in a dose-dependent manner. The antimicrobial properties of this protein were also confirmed with the use of Atomic Force Microscopy, which showed significant changes in the topology of different bacterial cell surfaces. Finally, when CSP16 was injected <i>in vivo</i> into <i>G. mellonella</i> larvae one hour after infection with <i>P. entomophila</i>, more survivors were observed at particular time-points. Taking into account its immune properties and putative ability to bind bacteria-derived compounds, the possible function of CSP16 in the host-pathogen interaction is discussed.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2471367"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524737","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":"Clinical analysis and risk factors associated with poor prognosis in nontuberculous mycobacterial infection.","authors":"Jinjing Chai, Sujie Zhang, Chong Ma, Qimin Mei, Tao Liu, Jihai Liu, Yecheng Liu, Huadong Zhu","doi":"10.1080/21505594.2025.2459313","DOIUrl":"10.1080/21505594.2025.2459313","url":null,"abstract":"<p><p>Recently, the incidence and prevalence of NTM have been increasing nationwide in many countries. This study aimed to identify risk factors associated with the prognosis and mortality of non-HIV nontuberculous mycobacterial disease patients. This retrospective study was conducted at Peking Union Medical College Hospital. The electronic medical records in the hospital's database from January 2013 to December 2022 were retrospectively reviewed. Relevant data, including clinical characteristics, laboratory findings, microbiological tests, treatments, and outcomes were collected and subjected to statistical analyses. The search identified 745 patients diagnosed with NTM infection, of whom 147 met the inclusion criteria. NTM pulmonary disease was the most commonly observed (<i>n</i> = 93; 63.3%), followed by disseminated infection (<i>n</i> = 43; 29.3%). The most frequent NTM species was <i>Mycobacterium avium</i> complex (55.8%), followed by <i>Mycobacterium abscessus</i> (21.2%). The incidence of <i>Aspergillus</i> and <i>Pseudomonas aeruginosa</i> infection was significantly higher in the NTM pulmonary disease group than in the disseminated NTM group. Cumulative mortality in the total patients was 24.49% at 5 years. High Charlson Comorbidity Index (CCI), high neutrophil-to-lymphocyte-ratio (NLR), haematological disease, and disseminated infection were identified as independent predictors of unfavourable outcomes. The area under the curve (AUC) values for NLR and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) were 0.751 and 0.763 with optimal cut-off values of 9.50 and 3.83, respectively, for prediction of mortality in patients with NTM disease.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2459313"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080926","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":"Gut microbiome composition and metabolic activity in metabolic-associated fatty liver disease.","authors":"Daya Zhang, Qi Wang, Da Li, Shiju Chen, Jinrun Chen, Xuli Zhu, Feihu Bai","doi":"10.1080/21505594.2025.2482158","DOIUrl":"10.1080/21505594.2025.2482158","url":null,"abstract":"<p><p>Metabolic Associated Fatty Liver Disease (MAFLD) impacts approximately 25% of the global population. Between April 2023 and July 2023, 60 patients with MAFLD, along with 60 age, ethnicity, and sex-matched healthy controls (HCs), were enrolled from the Inner Mongolia Autonomous Region, China. Analysis of gut microbiota composition and plasma metabolic profiles was conducted using metagenome sequencing and LC-MS. LEfSe analysis identified five pivotal species: Eubacterium rectale, Dialister invisus, Pseudoruminococcus massiliensis, GGB3278 SGB4328, and Ruminococcaceae bacteria. In subgroup analysis, Eubacterium rectale tended to increase by more than 2 times and more than double in the non-obese MAFLD group, and MAFLD with moderate hepatic steatosis (HS), respectively. Plasma samples identified 172 metabolites mainly composed of fatty acid metabolites such as propionic acid and butyric acid analogues. Ruminococcaceae bacteria have a strong positive correlation with β-alanine, uric acid, and L-valine. Pseudoruminococcus massiliensis has a strong positive correlation with β-alanine. Combinations of phenomics and metabolomics yielded the highest accuracy (AUC = 0.97) in the MAFLD diagnosis. Combinations of phenomics and metagenomics yielded the highest accuracy (AUC = 0.94) in the prediction of the MAFLD HS progress. Increases in Eubacterium rectale and decreases in Dialister invisus seem to be indicative of MAFLD patients. Eubacterium rectale may predict HS degree of MAFLD and play an important role in the development of non-obese MAFLD. Eubacterium rectale can generate more propionic acid and butyric acid analogues to absorb energy and increase lipid synthesis and ultimately cause MAFLD.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2482158"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693589","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":"Multifaceted quorum-sensing inhibiting activity of 3-(Benzo[d][1,3]dioxol-4-yl)oxazolidin-2-one mitigates <i>Pseudomonas aeruginosa</i> virulence.","authors":"Yi Wu, Fulong Wen, Shiyi Gou, Qiman Ran, Yiwen Chu, Wenbo Ma, Kelei Zhao","doi":"10.1080/21505594.2025.2479103","DOIUrl":"10.1080/21505594.2025.2479103","url":null,"abstract":"<p><p>As antibiotic resistance escalates into a global health crisis, novel therapeutic approaches against infectious diseases are in urgent need. <i>Pseudomonas aeruginosa</i>, an adaptable opportunistic pathogen, poses substantial challenges in treating a range of infections. The quorum-sensing (QS) system plays a pivotal role in orchestrating the production of a large set of virulence factors in a cell density-dependent manner, and the anti-virulence strategy targeting QS may show huge potential. Here, we present a comprehensive investigation into the potential of the synthesized compound 3-(benzo[d][1,3]dioxol-4-yl)oxazolidin-2-one (OZDO, C₁₀H₉NO₄) as a QS inhibitor to curb the virulence of <i>P. aeruginosa</i>. By employing an integrated approach encompassing <i>in silico</i> screening, <i>in vitro</i> and <i>in vivo</i> functional identification, we elucidated the multifaceted effects of OZDO. Molecular docking predicted that OZDO interfered with three core regulatory proteins of <i>P. aeruginosa</i> QS system. Notably, OZDO exhibited significant inhibition on the production of pyocyanin, rhamnolipid and extracellular proteases, biofilm formation, and cell motilities of <i>P. aeruginosa</i>. Transcriptomic analysis and quantitative real-time PCR displayed the down-regulation of QS-controlled genes in OZDO-treated PAO1, reaffirming the QS-inhibition activity of OZDO. <i>In vivo</i> assessments using a <i>Caenorhabditis elegans</i>-infection model demonstrated OZDO mitigated <i>P. aeruginosa</i> pathogenicity, particularly against the hypervirulent strain PA14. Moreover, OZDO in combination with polymyxin B and aztreonam presented a promising avenue for innovative anti-infective therapy. Our study sheds light on the multifaceted potential of OZDO as an anti-virulence agent and its significance in combating <i>P. aeruginosa</i>-associated infections.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2479103"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658883","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}