The nucleotide excision repair (NER) system of Helicobacter pylori: Role in mutation prevention and chromosomal import patterns after natural transformation

Abstract

BackgroundExtensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H. pylori mutation and recombination.ResultsInactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase) into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype.ConclusionsOur data suggest that the NER system has multiple functions in the genetic diversification of H. pylori, by contributing to its high mutation rate, and by controlling the incorporation of imported DNA fragments after natural transformation.

Genomic evolution and transmission of Helicobacter pylori in two South African families

“…Such variations in recombination rates have been previously described between lineages of S. enterica (32), E. coli (36), or Chlamydia trachomatis (37). For H. pylori, laboratory experiments have shown that recombination rates depended significantly on the combination of recipient and donor strains (11,13). Here, however, there seemed to be no relationship between infecting strain and effect of recombination.…”

“…This mechanism has been well studied through laboratory experiments (11)(12)(13). In vivo, extensive recombination was first detected by comparison of the phylogenetic signals of three gene fragments (14).…”

Persistence of Helicobacter pylori Infection: Genetic and Epigenetic Diversity

“…Mutants in nucleotide excision repair genes uvrA, uvrB, uvrC and uvrD have been constructed in H. pylori [49,72,73] and their UV sensitivity phenotype confirmed their role in DNA repair.…”

“…The scope of this chapter is to review H. pylori genetic and epigenetic plasticity and discuss the hypothesis that this plasticity promotes H. pylori adaptation to individual human hosts by generating phenotypically diverse populations. Emphasis has been put on mathematical modelling of H. pylori chronic infection [44], its micro-evolution and related mechanisms for the generation of diversity including genetic [45][46][47][48][49] and epigenetic diversity [50,51]. Mechanisms of horizontal gene transfer and the generation of intra-strain genetic diversity are reviewed and the implication of phasevarion-mediated epigenetic diversity is discussed in the context of bacterial population and adaption.…”

The core genome m5C methyltransferase JHP1050 (M.Hpy99III) plays an important role in orchestrating gene expression in Helicobacter pylori

“…H. pylori strains were cultured on blood agar plates (41), or in liquid cultures as described (9). Microaerobic conditions were generated in airtight jars (Oxoid, Wesel, Germany) with Anaerocult C gas producing bags (Merck, Darmstadt, Germany).…”