文献类型：期刊文献

英文题名：Direct sensing of host ferric iron by an archetype histidine kinase mediates virulence of an enteric pathogen

作者：Zhang, Yibei[1,2,3];Xiao, Gang[1];Ding, Haoyuan[2];Zou, Qian[2];Gu, Dan[4];Wen, Jiachen[5];Pei, Yonggang[1];Guo, Rongxian[1,6];Wang, Qiyao[2,3];Zhou, Xiaohui[1]

机构：[1]Southern Univ Sci & Technol, Sch Publ Hlth & Emergency Management, Div Microbiol, Shenzhen 518055, Guangdong, Peoples R China;[2]East China Univ Sci & Technol, Lab Aquat Anim Dis, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai 200237, Peoples R China;[4]Yangzhou Univ, Div Mol & Cellular Immunol & Infect, Jiangsu Key Lab Zoonosis, Yangzhou 225000, Peoples R China;[5]Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Dept Med Chem, Shenyang 110016, Peoples R China;[6]Henan Univ Sci & Technol, Coll Anim Sci & Technol, Dept Prevent Vet Med, Luoyang 471000, Peoples R China

年份：2025

卷号：122

期号：23

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001510624600001)】；

基金：This work was funded by Shenzhen Medical Research Fund (B2302024) , Guangdong Basic and Applied Basic Research Foundation (2023B1515120016) , Key Project of Shenzhen Science and Technology Innovation Commission (Grant No. JCYJ20220818100616034) , National Natural Science Foundation of China (32102850) and China Agriculture Research System of Ministry of Finance and Ministry of Agriculture and Rural Affairs (CARS-47) .

语种：英文

外文关键词：virulence; two-component system; bacteria; sensor; iron

摘要：Two-component system (TCS) histidine kinases enable bacterial pathogens to sense environmental signals and regulate adaptive responses during infection. The EnvZ/ OmpR TCS, known for its role in osmolarity/pH-dependent regulation of outer membrane porins across bacterial species, is also a central virulence regulator. However, the environmental cues that activate EnvZ/OmpR to trigger pathogenicity have remained unclear, limiting our understanding of host-pathogen interactions. Here, we demonstrate that in Vibrio parahaemolyticus, a major etiological agent of seafood-associated gastroenteritis, EnvZ functions as a direct ferric iron (Fe3+) sensor governing virulence programs. Fe3+-EnvZ interaction triggers kinase phosphorylation and activation, enabling transcriptional control of biofilm formation, swarming motility, and type 3/6 secretion systems. An iron-binding-deficient EnvZ mutant (EnvZQ103A) abrogated Fe3+ responsiveness and downstream signaling pathways. In an infant rabbit infection model, Fe3+ enhanced V. parahaemolyticus intestinal colonization and virulence through EnvZ/ OmpR signaling. This study identifies Fe3+ as the physiological ligand activating the EnvZ/OmpR virulence regulon and provides insight into how enteric pathogens exploit host-derived iron cues to promote infection.