Journal article
Octapeptin C4 and polymyxin resistance occur via distinct pathways in an epidemic XDR Klebsiella pneumoniae ST258 isolate
ME Pitt, MD Cao, MS Butler, S Ramu, D Ganesamoorthy, MAT Blaskovich, LJM Coin, MA Cooper
Journal of Antimicrobial Chemotherapy | OXFORD UNIV PRESS | Published : 2019
DOI: 10.1093/jac/dky458
Abstract
Background: Polymyxin B and E (colistin) have been pivotal in the treatment of XDR Gram-negative bacterial infections; however, resistance has emerged. A structurally related lipopeptide, octapeptin C4, has shown significant potency against XDR bacteria, including polymyxin-resistant strains, but its mode of action remains undefined. Objectives: We sought to compare and contrast the acquisition of resistance in an XDR Klebsiella pneumoniae (ST258) clinical isolate in vitro with all three lipopeptides to potentially unveil variations in their mode of action. Methods: The isolate was exposed to increasing concentrations of polymyxins and octapeptin C4 over 20 days. Day 20 strains underwentWGS,..
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Awarded by National Institutes of Health
Funding Acknowledgements
This research was supported by National Health and Medical Research Council (NHMRC) grants APP1005350 and APP1045326, and National Institutes of Health grant R21AI098731/R33AI098731-03. M. A. C. is an NHMRC Principal Research Fellow (APP1059354). L. J. M. C. is an Australian Research Council Future Fellow (FT110100972). M. E. P. is an Australian Postgraduate Award scholar. M. A. T. B. is supported in part by a Wellcome Trust Strategic Award (104797/Z/14/Z).