Bacterial hypermutation: clinical implications.

Abstract

Heritable hypermutation in bacteria is mainly due to alterations in the methyl-directed mismatch repair (MMR) system. MMR-deficient strains have been described from several bacterial species, and all of the strains exhibit increased mutation frequency and recombination, which are important mechanisms for acquired drug resistance in bacteria. Antibiotics select for drug-resistant strains and refine resistance determinants on plasmids, thus stimulating DNA recombination via the MMR system. Antibiotics can also act as indirect promoters of antibiotic resistance by inducing the SOS system and certain error-prone DNA polymerases. These alterations have clinical consequences in that efficacious treatment of bacterial infections requires high doses of antibiotics and/or a combination of different classes of antimicrobial agents. There are currently few new drugs with low endogenous resistance potential, and the development of such drugs merits further research.

• Authors: Anne Jolivet-Gougeon, Bela Kovacs, Sandrine Le Gall-David, Hervé Le Bars, Latifa Bousarghin, Martine Bonnaure-Mallet, Bernard Lobel, François Guillé, Claude-James Soussy, Peter Tenke
• Journal: Journal of medical microbiology (J Med Microbiol) Vol. 60 Issue Pt 5 Pg. 563-573 (May 2011) ISSN: 1473-5644 [Electronic] England
• PMID: 21349992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Topics

• Bacteria (drug effects, genetics, metabolism, pathogenicity)
• Bacterial Infections (drug therapy, microbiology)
• Cystic Fibrosis (microbiology)
• DNA Mismatch Repair (genetics)
• Drug Resistance, Bacterial (genetics)
• Foodborne Diseases (microbiology)
• Genes, Bacterial
• Humans
• Interspersed Repetitive Sequences
• Mutation
• Phenotype
• Prophages (genetics)
• Recombination, Genetic
• SOS Response, Genetics (genetics)
• Urinary Tract Infections (microbiology)
• Virulence (genetics)