Very recently, a new type of enzymatic system with methionine sulfoxide reductase activity has been found in some bacteria. It allows them to withstand hypochlorous acid (HOCl) stress such as that produced by the macrophages and neutrophils of our innate immune system to kill pathogens. Being able to repair the methionine residues of bacterial proteins massively oxidized by HOCl, this enzymatic system could play a major role in the virulence of certain pathogens. Studying its functioning will help to better understand the mechanisms of virulence and develop new types of antibiotics.

The researchers of the group Membrane & Pathogen [Institute of Structural Biology of Grenoble] and at our laboratory have initiated a detailed molecular characterization of this multi-partner MsrPQ system with methionine sulfoxide reductase (Msr) activity (Figure). For the first time, the researchers overproduced and purified the membrane component MsrQ in order to allow its characterization and composition (Figure legend). In this study, the flavin reductase Fre was identified as a cytosolic electron donor for this system, whereas to date only membrane quinones were reported to play such a role. It appears that these multiple sources of electrons, membranes and cytosolic, could constitute a major advantage allowing this system to effectively repair the cellular damages of HOCl.

The characterization of this system paves the way towards the search for specific inhibitors; the longer term prospects being the development of new types of antibiotics targeting this new system of defense against HOCl stress.