Jay Zhu
University of Pennsylvania Perelman School of Medicine, USA
Title: Cross-talk between oxidative stress and virulence optimizes multiple environmental transitions in Vibrio cholerae
Biography
Biography: Jay Zhu
Abstract
Bacterial pathogens must display versatility in gene expression to adapt to changing surroundings – especially to changes in the redox potential and the presence of redox-active compounds in the local microenvironment. For example, a key part of the life cycle of Vibrio cholerae, the causative agent of cholera, is the transition between oxygen-rich aquatic reservoirs to the oxygen-limiting environment of the human gastrointestinal tract, and combating reactive oxygen species (ROS) generated by the host immune system. Here using Tn-seq, we show that these two pathways – oxidative stress resistance and virulence – are linked in V. cholerae by two transcription factors, OhrR and AphB. We found that both OhrR and AphB bind to and regulate the promoters of the critical virulence activator tcpP and ROS resistance gene ohrA. In shifting between high-oxygen and low-oxygen environments, these proteins exhibit different kinetics of conformational change and binding at both promoters so as to optimize the expression of both genes. This cross-talk was critical both for colonizing the host and for bacterial survival upon exit into the environment. Our results suggest that regulation of bacterial virulence is closely intertwined with oxidative stress responses.