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.