{"title":"A c-di-GMP binding effector STM0435 modulates flagellar motility and pathogenicity in <i>Salmonella</i>.","authors":"Yuanji Dai, Ruirui Liu, Yingying Yue, Nannan Song, Haihong Jia, Zhongrui Ma, Xueyan Gao, Min Zhang, Xilu Yuan, Qing Liu, Xiaoyu Liu, Bingqing Li, Weiwei Wang","doi":"10.1080/21505594.2024.2331265","DOIUrl":null,"url":null,"abstract":"<p><p>Flagella play a crucial role in the invasion process of <i>Salmonella</i> and function as a significant antigen that triggers host pyroptosis. Regulation of flagellar biogenesis is essential for both pathogenicity and immune escape of <i>Salmonella</i>. We identified the conserved and unknown function protein STM0435 as a new flagellar regulator. The ∆<i>stm0435</i> strain exhibited higher pathogenicity in both cellular and animal infection experiments than the wild-type <i>Salmonella</i>. Proteomic and transcriptomic analyses demonstrated dramatic increases in almost all flagellar genes in the ∆<i>stm0435</i> strain compared to wild-type <i>Salmonella</i>. In a surface plasmon resonance assay, purified STM0435 protein-bound c-di-GMP had an affinity of ~8.383 µM. The crystal structures of apo-STM0435 and STM0435&c-di-GMP complex were determined. Structural analysis revealed that R33, R137, and D138 of STM0435 were essential for c-di-GMP binding. A <i>Salmonella</i> with STM1987 (GGDEF protein) or STM4264 (EAL protein) overexpression exhibits completely different motility behaviours, indicating that the binding of c-di-GMP to STM0435 promotes its inhibitory effect on <i>Salmonella</i> flagellar biogenesis.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978029/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virulence","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/21505594.2024.2331265","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Flagella play a crucial role in the invasion process of Salmonella and function as a significant antigen that triggers host pyroptosis. Regulation of flagellar biogenesis is essential for both pathogenicity and immune escape of Salmonella. We identified the conserved and unknown function protein STM0435 as a new flagellar regulator. The ∆stm0435 strain exhibited higher pathogenicity in both cellular and animal infection experiments than the wild-type Salmonella. Proteomic and transcriptomic analyses demonstrated dramatic increases in almost all flagellar genes in the ∆stm0435 strain compared to wild-type Salmonella. In a surface plasmon resonance assay, purified STM0435 protein-bound c-di-GMP had an affinity of ~8.383 µM. The crystal structures of apo-STM0435 and STM0435&c-di-GMP complex were determined. Structural analysis revealed that R33, R137, and D138 of STM0435 were essential for c-di-GMP binding. A Salmonella with STM1987 (GGDEF protein) or STM4264 (EAL protein) overexpression exhibits completely different motility behaviours, indicating that the binding of c-di-GMP to STM0435 promotes its inhibitory effect on Salmonella flagellar biogenesis.
期刊介绍:
Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication.
Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.