Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori

Among the several factors that affect the appearance and spread of acquired antibiotic resistance, the mutation frequency and the biological cost of r esistance are of special importance. Measurements of the mutation frequency to rifampicin resistance in Helicobacter pylori strains isolated from dysp eptic patients showed that approximate to1/4 of the isolates had higher mut ation frequencies than Enterobacteriaceae mismatch-repair defective mutants . This high mutation frequency could explain why resistance is so frequentl y acquired during antibiotic treatment of H. pylori infections. Inactivatio n of the mutS gene had no substantial effect on the mutation frequency, sug gesting that MutS-dependent mismatch repair is absent in this bacterium. Fu rthermore, clarithromycin resistance conferred a biological cost, as measur ed by a decreased competitive ability of the resistant mutants in mice. In clinical isolates this cost could be reduced, indicating that compensation is a clinically relevant phenomenon that could act to stabilize resistant b acteria in a population.