Salmonella Typhimurium uses the Cpx stress response to detect N-chlorotaurine and promote the repair of oxidized proteins

The cell envelope of gram-negative bacteria constitutes the first protective barrier between a cell and its environment. During host infection, the bacterial envelope is subjected to several stresses, including those induced by reactive oxygen species (ROS) and reactive chlorine species (RCS) produced by immune cells. Among RCS, N-chlorotaurine (N-ChT), which results from the reaction between hypochlorous acid and taurine, is a powerful and less diffusible oxidant. Here, using a genetic approach, we demonstrate that Salmonella Typhimurium uses the CpxRA two-component system to detect N-ChT oxidative stress. Moreover, we show that periplasmic methionine sulfoxide reductase (MsrP) is part of the Cpx regulon. Our findings demonstrate that MsrP is required to cope with N-ChT stress by repairing N-ChT-oxidized proteins in the bacterial envelope. By characterizing the molecular signal that induces Cpx when S. Typhimurium is exposed to N-ChT, we show that N-ChT triggers Cpx in an NlpE-dependent manner. Thus, our work establishes a direct link between N-ChT oxidative stress and the envelope stress response.