The Helicobacter pylori MutS protein confers protection from oxidative DNA damage

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Abstract
Summary: The human gastric pathogenic bacterium Helicobacter pylori lacks a MutSLH‐like DNA mismatch repair system. Here, we have investigated the functional roles of a mutS homologue found in H. pylori, and show that it plays an important physiological role in repairing oxidative DNA damage. H. pylori mutS mutants are more sensitive than wild‐type cells to oxidative stress induced by agents such as H2O2, paraquat or oxygen. Exposure of mutS cells to oxidative stress results in a significant (∼10‐fold) elevation of mutagenesis. Strikingly, most mutations in mutS cells under oxidative stress condition are G:C to T:A transversions, a signature of 8‐oxoguanine (8‐oxoG). Purified H. pylori MutS protein binds with a high specific affinity to double‐stranded DNA (dsDNA) containing 8‐oxoG as well as to DNA Holliday junction structures, but only weakly to dsDNA containing a G:A mismatch. Under oxidative stress conditions, mutS cells accumulate higher levels (approximately threefold) of 8‐oxoG DNA lesions than wild‐type cells. Finally, we observe that mutS mutant cells have reduced colonization capacity in comparison to wild‐type cells in a mouse infection model.