Role of DNA base excision repair in the mutability and virulence of Streptococcus mutans.
The oral pathogen, Streptococcus mutans, possesses inducible DNA repair defences for protection against pH fluctuations and production of reactive oxygen metabolites such as hydrogen peroxide (H(2) O(2) ), which are present in the oral cavity. DNA base excision repair (BER) has a critical role in genome maintenance by preventing the accumulation of mutations associated with environmental factors and normal products of cellular metabolism. In this study, we examined the consequences of compromising the DNA glycosylases (Fpg and MutY) and endonucleases (Smx and Smn) of the BER pathway and their relative role in adaptation and virulence. Enzymatic characterization of the BER system showed that it protects the organism against the effects of the highly mutagenic lesion, 7,8-dihydro-8-oxo-2'-deoxyguanine (8-oxo-dG). S. mutans strains lacking a functional Fpg, MutY or Smn showed elevated spontaneous mutation frequencies; and, these mutator phenotypes correlated with the ability of the strains to survive killing by acid and oxidative agents. In addition, in the Galleria mellonella virulence model, strains of S. mutans deficient in Fpg, MutY and Smn showed increased virulence as compared with the parent strain. Our results suggest that, for S. mutans, mutator phenotypes, due to loss of BER enzymes, may confer an advantage to virulence of the organism.
Department of Microbiology and Immunology             Center for Oral Biology, University of Rochester, Rochester, NY 14642, USA.
Kaisha
K
Gonzalez
Roberta C
RC
Faustoferri
Robert G
RG
Quivey
D000143:Acids / Q000633:toxicity; D000818:Animals; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007915:Lepidoptera / Q000382:microbiology; D050296:Microbial Viability / Q000187:drug effects; D018384:Oxidative Stress; D013295:Streptococcus mutans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D013312:Stress, Physiological; D016019:Survival Analysis; D014774:Virulence
D000143:Acids; D004269:DNA, Bacterial; D045643:DNA Repair Enzymes