Thiol-based switch mechanism of virulence regulator AphB modulates oxidative stress response in Vibrio cholerae.
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.
Department of Biotechnology, Huazhong University of Science and Technology, Wuhan, China.|Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Zhi
Z
Liu
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.|Department of Microbiology, Nanjing Agricultural University, Nanjing, 210095, China.
Hui
H
Wang
Division of Microbiology, Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
Zhigang
Z
Zhou
Department of Microbiology, Nanjing Agricultural University, Nanjing, 210095, China.|Division of Bacterial Infectious Diseases, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
Ying
Y
Sheng
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nawar
N
Naseer
Division of Bacterial Infectious Diseases, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
Biao
B
Kan
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Jun
J
Zhu
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
C120327:AphB protein, Vibrio cholerae; D001426:Bacterial Proteins; D012097:Repressor Proteins; D013438:Sulfhydryl Compounds; D015534:Trans-Activators; D014157:Transcription Factors