Hypermutation as a Factor Contributing to the Acquisition of Antimicrobial Resistance

Contrary to what was thought previously, bacteria seem to be, not merely spectators to their own evolution, but, through a variety of mechanisms, able to increase the rate at which mutations occur and, consequently, to increase their chances of becoming resistant to antibiotics. Laboratory studies and mathematical models suggest that, under stressful conditions, such as antibiotic challenge, selective pressure favors mutator strains of bacteria over nonmutator strains. These hypermutable strains have been found in natural bacterial populations at higher frequencies than expected. The presence of mutator strains in the clinical setting may indicate an enhanced risk of acquiring antibiotic resistance through mutational and recombinational events. In addition, some antibiotics are inducers of mechanisms that transiently increase the mutation rate, and thus probably act, not only as mere selectors of antibiotic resistant clones, but also as resistance-promoters.