Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment

Ryo Kinoshita-Daitoku, Kotaro Kiga, Takahito Sanada, Yoshitoshi Ogura, Zhu Bo, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Mototsugu Tanaka, Arpana Sood, Toshihiko Suzuki, Kenta Nakai, Tetsuya Hayashi, Hitomi Mimuro

Research output: Contribution to journalArticle

Abstract

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 (ΔuvrA, ΔuvrB, ΔruvA, Δnth, ΔmutY, ΔmutS, and Δung). We performed susceptibility testing to rifampicin in vitro and found that ΔmutY exhibited the highest mutation frequency among the mutants. The number of bacteria colonizing the stomach was significantly lower with ΔmutY 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 ΔmutY strains exhibited a high frequency of spontaneous G:C to T:A mutations. However, the frequency of phase variations in the ΔmutY 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.

Original languageEnglish
Pages (from-to)806-811
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume525
Issue number3
DOIs
Publication statusPublished - May 7 2020

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Kinoshita-Daitoku, R., Kiga, K., Sanada, T., Ogura, Y., Bo, Z., Iida, T., Yokomori, R., Kuroda, E., Tanaka, M., Sood, A., Suzuki, T., Nakai, K., Hayashi, T., & Mimuro, H. (2020). Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment. Biochemical and Biophysical Research Communications, 525(3), 806-811. https://doi.org/10.1016/j.bbrc.2020.02.087