Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus.
Fusidic acid resistance resulting from mutations in elongation factor G (EF-G) of Staphylococcus aureus is associated with fitness costs during growth in vivo and in vitro. In both environments, these costs can be partly or fully compensated by the acquisition of secondary intragenic mutations. Among clinical isolates of S. aureus, fusidic acid-resistant strains have been identified that carry multiple mutations in EF-G at positions similar to those shown experimentally to cause resistance and fitness compensation. This observation suggests that fitness-compensatory mutations may be an important aspect of the evolution of antibiotic resistance in the clinical environment, and may contribute to a stabilization of the resistant bacteria present in a bacterial population.
Nagaev
I
I
Department of Cell and Molecular Biology, Box 596, Biomedical Center, S-751 24 Uppsala, Sweden.
Björkman
J
J
Andersson
D I
DI
Hughes
D
D
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D019143:Evolution, Molecular; D005672:Fusidic Acid / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020653:Peptide Elongation Factor G / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020653:Peptide Elongation Factor G; D005672:Fusidic Acid