Two-component systems (TCS) are signalling pathways that allow bacterial cells to sense, respond and adapt to fluctuating environments. Among the classical TCS of
Escherichia coli
, HprSR has recently been shown to be involved in the regulation of
msrPQ
, which encodes the periplasmic methionine sulfoxide reductase system. In this study, we demonstrate that hypochlorous acid (HOCl) induces the expression of
msrPQ
in an HprSR-dependant manner, whereas H
2
O
2
, NO and paraquat (a superoxide generator) do not. Therefore, HprS appears to be an HOCl-sensing histidine kinase. Using a directed mutagenesis approach, we show that Met residues located in the periplasmic loop of HprS are important for its activity: as HOCl preferentially oxidizes Met residues, we provide evidence that HprS could be activated via the reversible oxidation of its methionine residues, meaning that MsrPQ plays a role in switching HprSR off. We propose that the activation of HprS by HOCl could occur through a Met redox switch. HprSR appears to be the first characterized TCS able to detect reactive chlorine species (RCS) in
E. coli
. This study represents an important step towards understanding the mechanisms of RCS resistance in prokaryotes.
IMPORTANCE
Understanding how bacteria respond to oxidative stress at the molecular level is crucial in the fight against pathogens. HOCl is one of the most potent industrial and physiological microbiocidal oxidants. Therefore bacteria have developed counterstrategies to survive HOCl-induced stress. Over the last decade, important insights into these bacterial protection factors have been obtained. Our work establishes HprSR as a reactive chlorine species-sensing, two-component system in
Escherichia coli
MG1655, which regulates the expression of MsrPQ, a repair system for HOCl-oxidized proteins. Moreover we provide evidence suggesting that HOCl could activate HprS through a methionine redox switch.
A thiol-based intramolecular redox switch in four-repeat tau controls fibril assembly and disassembly
