A paradigm for direct stress-induced mutation in prokaryotes

FASEB J. 2006 Dec;20(14):2476-85. doi: 10.1096/fj.06-6209com.

Abstract

Environmental stresses may lead to selection for hypermutator bacterial cells, which have an increased chance of generating beneficial variants. With stress removal, cost of mutation exceeds the fitness advantage, selecting against hypermutators. Hypermutators arise through several mechanisms, including inactivation of mismatch repair genes (MMR) or induction of error-prone polymerases. Helicobacter pylori may provide an alternative mechanism of stress-induced mutagenesis, since it lacks the MMR genes and error-prone polymerases found in other bacterial species, and possesses an endogenously high mutation frequency. In this study, we expose H. pylori strains to reactive oxygen species and reactive nitrogen species, stressors found in their natural environment. These exposures directly resulted in elevated rates of spontaneous point mutation, deletion between direct repeats, and intergenomic recombination. We demonstrate that these effects are transient and do not involve selection for hypermutator strains. That H. pylori possesses direct repeats in regions where potential gene rearrangements can occur suggests a mechanism for targeted mutation in response to stress that avoids the deleterious fitness costs of fixed hypermutation. These studies provide a new paradigm for adaptation under increased selective pressures that may be present in other prokaryotes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA Damage / drug effects
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / drug effects
  • DNA, Bacterial / genetics
  • Gene Deletion
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / metabolism
  • Mutagenesis* / drug effects
  • Mutation / genetics*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics*
  • Reactive Nitrogen Species / metabolism
  • Reactive Nitrogen Species / pharmacology
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology

Substances

  • DNA, Bacterial
  • Reactive Nitrogen Species
  • Reactive Oxygen Species