Direct sensing of host ferric iron by an archetype histidine kinase mediates virulence of an enteric pathogen

• 成果类型: Article
• 署名作者: Zhang, Yibei; Xiao, Gang; Ding, Haoyuan; Zou, Qian; Gu, Dan; Wen, Jiachen; Pei, Yonggang; Guo, Rongxian; Wang, Qiyao; Zhou, Xiaohui
• 署名单位: Southern University of Science & Technology; East China University of Science & Technology; Yangzhou University; Shenyang Pharmaceutical University; Henan University of Science & Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12908
• DOI: 10.1073/pnas.2507874122
• 发表日期: 2025-06-10
• 关键词: vibrio-parahaemolyticus; escherichia-coli; gene-expression; ompc genes; systems; osmoregulation; colonization; exsa; seq

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.