Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons

The identification of an enzymatic system repairing proteins containing oxidized methionine in the bacterial cell envelope, a compartment particularly susceptible to oxidative damage by host defence mechanisms. A novel repair system for oxidative damage Frédéric Barras and colleagues report the identification of an enzyme system, MsrPQ, which repairs a wide range of periplasmic proteins with oxidatively damaged methionine (methionine sulfoxide, Met-O) in the bacterial cell envelope, a compartment that is particularly susceptible to oxidative damage by host defence mechanisms. MsrP and MsrQ are widely distributed in Gram-negative bacteria and are expressed following exposure to hypochlorous acid, a powerful antimicrobial agent that is released by neutrophils. Interestingly, the MsrPQ repair system is functionally distinct from conventional methionine sulfoxide reductases as it exhibits non-stereospecificity and can reduce both R - and S -diastereoisomers of Met-O. Furthermore, the authors report a novel mechanism of action for MsrPQ in which electrons from the respiratory chain are used for reducing power, establishing a new link between metabolism and cellular integrity. The reactive species of oxygen and chlorine damage cellular components, potentially leading to cell death. In proteins, the sulfur-containing amino acid methionine is converted to methionine sulfoxide, which can cause a loss of biological activity. To rescue proteins with methionine sulfoxide residues, living cells express methionine sulfoxide reductases (Msrs) in most subcellular compartments, including the cytosol, mitochondria and chloroplasts 1 , 2 , 3 . Here we report the identification of an enzymatic system, MsrPQ, repairing proteins containing methionine sulfoxide in the bacterial cell envelope, a compartment particularly exposed to the reactive species of oxygen and chlorine generated by the host defence mechanisms. MsrP, a molybdo-enzyme, and MsrQ, a haem-binding membrane protein, are widely conserved throughout Gram-negative bacteria, including major human pathogens. MsrPQ synthesis is induced by hypochlorous acid, a powerful antimicrobial released by neutrophils. Consistently, MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing a wide series of structurally unrelated periplasmic proteins from methionine oxidation, including the primary periplasmic chaperone SurA. For this activity, MsrPQ uses electrons from the respiratory chain, which rep