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bioRxiv · 10.1101/2021.09.09.459708

HypVW is an HOCl-Sensing Two Component System in Escherichia coli

El Hajj, S.·Henry, C.·Vergnes, A.·Loiseau, L.·Gael, B.·Barre, R.·Aussel, L.·Ezraty, B.
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Abstract

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, YedVW has been recently showed to be involved in the regulation of msrPQ, encoding for the periplasmic methionine sulfoxide reductase system. In this study, we demonstrate that hypochlorous acid (HOCl) induces the expression of msrPQ in a YedVW dependant manner, whereas H2O2, NO and paraquat (a superoxide generator) do not. Therefore, YedV appears to be an HOCl-sensing histidine kinase. Based on this finding, we proposed to rename this system HypVW. Moreover, using a directed mutagenesis approach, we show that Met residues located in the periplasmic loop of HypV (formerly YedV) are important for its activity. Given that HOCl oxidizes preferentially Met residues, we bring evidences that HypV could be activated via the reversible oxidation of its methionine residues, thus conferring to MsrPQ a role in switching HypVW off. Based on these results, we propose that the activation of HypV by HOCl could occur through a Met redox switch. HypVW appears to be the first characterized TCS able to detect HOCl in E. coli. This study represents an important step in understanding the mechanisms of reactive chlorine species resistance in prokaryotes. IMPORTANCEUnderstanding molecularly how bacteria respond to oxidative stress is crucial to fight pathogens. HOCl is one of the most potent industrial and physiological microbiocidal oxidant. 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 HypVW as an HOCl-sensing two component system in Escherichia coli MG1655 which regulates the expression of the periplasmic HOCl-oxidized proteins repair system MsrPQ. Moreover we bring evidences suggesting that HOCl could activate HypV through a methionine redox switch.

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El Hajj, S., Henry, C., Vergnes, A., Loiseau, L., Gael, B., Barre, R., Aussel, L., Ezraty, B.. 2021-09-12. HypVW is an HOCl-Sensing Two Component System in Escherichia coli. https://doi.org/10.1101/2021.09.09.459708

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