title: Unacylated tridecaptin A₁ acts as an effective sensitiser of Gram-negative bacteria to other antibiotics.
abstract: A derivative of the linear cationic lipopeptide tridecaptin A₁missing the N-terminal lipophilic acyl group, termed H-TriA₁, is devoid of antimicrobial activity but is extremely effective at sensitising Gram-negative bacteria to certain antibiotics. H-TriA₁has low cytotoxicity compared with the natural peptide and in low concentrations it can substantially lower the minimum inhibitory concentration (MIC) of some antibiotics against strains of Escherichia coli, Campylobacter jejuni and Klebsiella pneumoniae. In particular, the MIC of rifampicin was lowered 256-512-fold against K. pneumoniae strains using low concentrations of H-TriA₁. H-TriA₁does not exert its synergistic effect through partial membrane lysis, but does bind to model bacterial membranes in a manner akin to the natural peptide. Formation of this stable secondary structure on the outer membrane may account for the observed synergistic activity.
authors.affiliation: Department of Chemistry, University of Alberta, 30 University Campus NW, Edmonton, AB, Canada T6G 2G2.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Cochrane
authors.affiliation: Department of Chemistry, University of Alberta, 30 University Campus NW, Edmonton, AB, Canada T6G 2G2. Electronic address: john.vederas@ualberta.ca.
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016123:Campylobacter jejuni / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D055666:Lipopeptides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D055666:Lipopeptides; D010455:Peptides; C017770:tridecaptins; D014640:Vancomycin; D012293:Rifampin
keywords: Antibiotic; Gram-negative bacteria; Lipopeptide; Rifampicin; Tridecaptin; Vancomycin