title: Generation of ramoplanin-resistant Staphylococcus aureus.
abstract: Ramoplanin is a lipoglycodepsipeptide antimicrobial active against clinically important Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. To proactively examine ramoplanin resistance, we subjected S. aureus NCTC 8325-4 to serial passage in the presence of increasing concentrations of ramoplanin, generating the markedly resistant strain RRSA16. Susceptibility testing of RRSA16 revealed the unanticipated acquisition of cross-resistance to vancomycin and nisin. RRSA16 displayed phenotypes, including a thickened cell wall and reduced susceptibility to Triton X-100-induced autolysis, which are associated with vancomycin intermediate-resistant S. aureus strains. Passage of RRSA16 for 18 days in a drug-free medium yielded strain R16-18d with restored antibiotic susceptibility. The RRSA16 isolate may be used to identify the genetic and biochemical basis for ramoplanin resistance and to further our understanding of the evolution of antibiotic cross-resistance mechanisms in S. aureus.
authors.affiliation: Department of Chemistry, Duke University, Durham, NC, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Schmidt
authors.forename: Adrienne
authors.initials: A
authors.lastname: Greenough
authors.forename: Michelle
authors.initials: M
authors.lastname: Burns
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Luteran
authors.forename: Dewey G
authors.initials: DG
authors.lastname: McCafferty
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall; D047630:Depsipeptides / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009561:Nisin / Q000494:pharmacology; D017830:Octoxynol / Q000494:pharmacology; D010641:Phenotype; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D003902:Detergents; C041438:ramoplanin; D009561:Nisin; D014640:Vancomycin; D017830:Octoxynol