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.