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Thiol‐based switch mechanism of virulence regulator AphB modulates oxidative stress response in Vibrio cholerae
Author(s) -
Liu Zhi,
Wang Hui,
Zhou Zhigang,
Sheng Ying,
Naseer Nawar,
Kan Biao,
Zhu Jun
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13524
Subject(s) - vibrio cholerae , biology , virulence , microbiology and biotechnology , regulator , activator (genetics) , gene , reactive oxygen species , oxidative stress , regulation of gene expression , bacteria , biochemistry , genetics
Summary Bacterial pathogens display versatile gene expression to adapt to changing surroundings. For example, Vibrio cholerae , the causative agent of cholera, utilizes distinct genetic programs to combat reactive oxygen species (ROS) in aquatic environments or during host infection. We previously reported that the virulence activator AphB in V. cholerae is involved in ROS resistance. Here by performing a genetic screen, we show that AphB represses ROS resistance gene ohrA , which is also repressed by another regulator, OhrR. Reduced forms of both AphB and OhrR directly bind to the ohrA promoter and repress its expression, whereas organic hydroperoxides such as cumene hydroperoxide (CHP) deactivate AphB and OhrR. OhrA is critical for V. cholerae adult mouse colonization but is dispensable when the mice are treated with antioxidants. Furthermore, similar to our previous finding that AphB and OhrR exhibit different reduction rates during the shift from oxic to anoxic environments, we found that AphB is also oxidized more slowly than OhrR under peroxide stress or exposure to oxygen. This differential regulation optimizes the expression of ohrA and contributes to V. cholerae's ability to survive in a variety of environmental niches that contain different levels of ROS.