title: Fitness cost of chromosomal drug resistance-conferring mutations.
abstract: To study the cost of chromosomal drug resistance mutations to bacteria, we investigated the fitness cost of mutations that confer resistance to different classes of antibiotics affecting bacterial protein synthesis (aminocyclitols, 2-deoxystreptamines, macrolides). We used a model system based on an in vitro competition assay with defined Mycobacterium smegmatis laboratory mutants; selected mutations were introduced by genetic techniques to address the possibility that compensatory mutations ameliorate the resistance cost. We found that the chromosomal drug resistance mutations studied often had only a small fitness cost; compensatory mutations were not involved in low-cost or no-cost resistance mutations. When drug resistance mutations found in clinical isolates were considered, selection of those mutations that have little or no fitness cost in the in vitro competition assay seems to occur. These results argue against expectations that link decreased levels of antibiotic consumption with the decline in the level of resistance.
authors.affiliation: Institut für Medizinische Mikrobiologie, Universität Zürich, CH-8028 Zürich, Switzerland. psander@immv.unizh.ch
authors.forename: Peter
authors.initials: P
authors.lastname: Sander
authors.forename: Burkhard
authors.initials: B
authors.lastname: Springer
authors.forename: Therdsak
authors.initials: T
authors.lastname: Prammananan
authors.forename: Antje
authors.initials: A
authors.lastname: Sturmfels
authors.forename: Martin
authors.initials: M
authors.lastname: Kappler
authors.forename: Michel
authors.initials: M
authors.lastname: Pletschette
authors.forename: Erik C
authors.initials: EC
authors.lastname: Böttger
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002876:Chromosomes, Bacterial / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D012269:Ribosomal Proteins / Q000235:genetics; D012641:Selection, Genetic; D013307:Streptomycin / Q000494:pharmacology; D012407:rRNA Operon / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D012269:Ribosomal Proteins; C034212:ribosomal protein S12; D013307:Streptomycin