The Helicobacter pylori MutS protein confers protection from oxidative DNA damage

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 ( similar to 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 wildtype cells in a mouse infection model.