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Evolution in fast forward: a potential role for mutators in accelerating Staphylococcus aureus pathoadaptation.

Abstract
Pathogen evolution and subsequent phenotypic heterogeneity during chronic infection are proposed to enhance Staphylococcus aureus survival during human infection. We tested this theory by genetically and phenotypically characterizing strains with mutations constructed in the mismatch repair (MMR) and oxidized guanine (GO) system, termed mutators, which exhibit increased spontaneous-mutation frequencies. Analysis of these mutators revealed not only strain-dependent increases in the spontaneous-mutation frequency but also shifts in mutational type and hot spots consistent with loss of GO or MMR functions. Although the GO and MMR systems are relied upon in some bacterial species to prevent reactive oxygen species-induced DNA damage, no deficit in hydrogen peroxide sensitivity was found when either of these DNA repair pathways was lost in S. aureus. To gain insight into the contribution of increased mutation supply to S. aureus pathoadaptation, we measured the rate of α-hemolysin and staphyloxanthin inactivation during serial passage. Detection of increased rates of α-hemolysin and staphyloxanthin inactivation in GO and MMR mutants suggests that these strains are capable of modifying virulence phenotypes implicated in mediating infection. Accelerated derivation of altered virulence phenotypes, combined with the absence of increased ROS sensitivity, highlights the potential of mutators to drive pathoadaptation in the host and serve as catalysts for persistent infections.
AuthorsGregory S Canfield, Johanna M Schwingel, Matthew H Foley, Kelly L Vore, Kanitsak Boonanantanasarn, Ann L Gill, Mark D Sutton, Steven R Gill
JournalJournal of bacteriology (J Bacteriol) Vol. 195 Issue 3 Pg. 615-28 (Feb 2013) ISSN: 1098-5530 [Electronic] United States
PMID23204459 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Toxins
  • DNA, Bacterial
  • Hemolysin Proteins
  • Reactive Oxygen Species
  • Virulence Factors
  • Xanthophylls
  • staphylococcal alpha-toxin
  • Guanine
  • staphyloxanthin
  • Hydrogen Peroxide
Topics
  • Adaptation, Physiological (genetics)
  • Bacterial Toxins (genetics, metabolism)
  • Base Sequence
  • DNA Damage
  • DNA Mismatch Repair (genetics)
  • DNA, Bacterial (genetics)
  • Gene Expression Regulation, Bacterial (physiology)
  • Guanine (metabolism)
  • Hemolysin Proteins (genetics, metabolism)
  • Hydrogen Peroxide
  • Molecular Sequence Data
  • Mutation
  • Oxidation-Reduction
  • Reactive Oxygen Species
  • Staphylococcus aureus (genetics, metabolism, physiology)
  • Time Factors
  • Virulence Factors (biosynthesis, genetics)
  • Xanthophylls (genetics, metabolism)

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