Biochemical and Biophysical Research Communications, Vol.525, No.3, 806-811, 2020
Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment
Helicobacter pylori, a pathogenic bacterium that colonizes in the human stomach, harbors DNA repair genes to counter the gastric environment during chronic infection. In addition, H. pylori adapts to the host environment by undergoing antigenic phase variation caused by genomic mutations. The emergence of mutations in nucleotide sequences is one of the major factors underlying drug resistance and genetic diversity in bacteria. However, it is not clear how DNA repair genes contribute to driving the genetic change of H. pylori during chronic infection. To elucidate the physiological roles of DNA repair genes, we generated DNA repair-deficient strains of H. pylori (Delta uvrA, Delta uvrB, Delta ruvA, Delta nth, Delta mutY, Delta mutS, and Delta ung). We performed susceptibility testing to rifampicin in vitro and found that Delta mutY exhibited the highest mutation frequency among the mutants. The number of bacteria colonizing the stomach was significantly lower with Delta mutY strain compared with wild-type strains in a Mongolian gerbil model of H. pylori infection. Furthermore, we performed a genomic sequence analysis of the strains isolated from the Mongolian gerbil stomachs eight weeks after infection. We found that the isolated Delta mutY strains exhibited a high frequency of spontaneous G:C to T:A mutations. However, the frequency of phase variations in the Delta mutY strain was almost similar to the wild-type strain. These results suggest that MutY may play a role in modes of gastric environmental adaptation distinct from phase variation. (C) 2020 Elsevier Inc. All rights reserved.