title: Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori.
abstract: Among the several factors that affect the appearance and spread of acquired antibiotic resistance, the mutation frequency and the biological cost of resistance are of special importance. Measurements of the mutation frequency to rifampicin resistance in Helicobacter pylori strains isolated from dyspeptic patients showed that approximately 1/4 of the isolates had higher mutation frequencies than Enterobacteriaceae mismatch-repair defective mutants. This high mutation frequency could explain why resistance is so frequently acquired during antibiotic treatment of H. pylori infections. Inactivation of the mutS gene had no substantial effect on the mutation frequency, suggesting that MutS-dependent mismatch repair is absent in this bacterium. Furthermore, clarithromycin resistance conferred a biological cost, as measured 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 bacteria in a population.
authors.affiliation: Swedish Institute for Infectious Disease Control, 17182 Solna, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Björkholm
authors.forename: M
authors.initials: M
authors.lastname: Sjölund
authors.forename: P G
authors.initials: PG
authors.lastname: Falk
authors.forename: O G
authors.initials: OG
authors.lastname: Berg
authors.forename: L
authors.initials: L
authors.lastname: Engstrand
authors.forename: D I
authors.initials: DI
authors.lastname: Andersson
mesh_terms: D000251:Adenosine Triphosphatases; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D020137:Base Pair Mismatch; D017291:Clarithromycin / Q000494:pharmacology; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D051719:MutS DNA Mismatch-Binding Protein; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D007983:Lewis Blood Group Antigens; D000251:Adenosine Triphosphatases; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli; D017291:Clarithromycin; D012293:Rifampin