The role of mutators in the emergence of antibiotic-resistant bacteria.

CHOPRA, Ian, O'NEILL, Alexander J and MILLER, Keith (2003). The role of mutators in the emergence of antibiotic-resistant bacteria. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 6 (3), 137-145.

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Bacteria contain a number of error prevention and error correction systems that maintain genome stability. However, strains exhibiting elevated mutation frequencies have recently been reported amongst natural populations of pathogenic Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, Neisseria meningitidis, Helicobacter pylori and Streptococcus pneumoniae. The majority of naturally occurring, strong mutators contain defects in the methyl-directed mismatch repair (MMR) system, with mutations in mutS predominating. MMR-deficient strains possess superior genetic backgrounds for the selection of some antibiotic-resistance mutations since mutation frequencies up to 1000-fold higher than normal strains have been reported, and resistance levels achieved in mutators can be greater than those arising in non-mutator hosts. MMR is a major constraint to interspecies recombination events. Removal of this barrier, as in the case of MMR defective mutators, also enhances the frequency of horizontal gene transfer, which is an important mechanism of acquired drug resistance in bacteria. Permanent global mutator status is associated with loss of fitness as mutators accumulate deleterious mutations more frequently than non-mutators. Fitness limitations of mutators may be overcome simply by the high bacterial cell densities that can be achieved during acute infection or by the adoption of transient mutator status. Mutators are a risk factor during the treatment of bacterial infections as they appear to enhance the selection of mutants expressing high- and low-level antibiotic resistance and have the capacity to refine existing plasmid-located resistance determinants.

Item Type: Article
Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomedical Research Centre
Identification Number:
Page Range: 137-145
Depositing User: Jamie Young
Date Deposited: 01 Jun 2015 11:22
Last Modified: 18 Mar 2021 18:45

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