title: Loss of function of the gdpP protein leads to joint β-lactam/glycopeptide tolerance in Staphylococcus aureus.
abstract: The genetic basis of tolerance to inhibitors of peptidoglycan biosynthesis in Staphylococcus aureus was investigated by generating tolerant mutants in vitro and characterizing them by comparative genome sequencing. Two independently selected tolerant mutants harbored nonsynonymous mutations in gdpP, a gene encoding a putative membrane-located signaling protein. Insertional inactivation of gdpP also conferred tolerance. Our findings further implicate altered signal transduction as a route to antibiotic tolerance in S. aureus.
authors: Antimicrobial Research Centre and Institute of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.
authors: J M
authors: JM
authors: Griffiths
authors: A J
authors: AJ
authors: O'Neill
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004269:DNA, Bacterial; D024881:Drug Resistance, Bacterial; D020868:Gene Silencing; D006020:Glycopeptides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D016254:Mutagenesis, Insertional; D009154:Mutation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000235:genetics; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D006020:Glycopeptides; D047090:beta-Lactams