Cross-resistance to human cationic antimicrobial peptides and to polymyxins mediated by the plasmid-encoded MCR-1?

• Published in: Clinical microbiology and infection Vol. 23; no. 9; pp. 676.e1 - 676.e5
• Main Authors: Dobias, J., Poirel, L., Nordmann, P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2017
• Subjects: Antimicrobial Cationic Peptides - pharmacology; colistin; Colistin - pharmacology; defensins; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; Enterobacteriaceae; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli Infections - microbiology; Escherichia coli Proteins - genetics; Humans; Klebsiella Infections - microbiology; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; MCR-1; Polymyxins - pharmacology; defensins; MCR-1; Escherichia coli; colistin; Klebsiella pneumoniae; Enterobacteriaceae
• ISSN: 1198-743X; 1469-0691
• DOI: 10.1016/j.cmi.2017.03.015

To evaluate whether acquired resistance to cationic antimicrobial peptide (CAMP) group molecules, being normal components of the human immune system, may select co-resistance to antibiotic peptides such as polymyxins, considering they share the same mechanism of action. We aimed to evaluate strains producing the recently identified plasmid-encoded polymyxin resistance determinant MCR-1, which is a phosphoethanolamine transferase that modifies the lipopolysaccharide structure of Gram-negative bacteria.
In vitro susceptibility studies were performed using human CAMPs, namely cathelicidin LL-37, α-defensin 5 (HD5), and β-defensin 3 (HDB3), towards MCR-1-producing and colistin-resistant Escherichia coli or Klebsiella pneumoniae.
Cross-resistance to CAMPs and colistin mediated by MCR-1 or chromosomal mechanisms was neither observed in E. coli nor in K. pneumoniae.
Future therapeutic development of human CAMPs is not likely to be impeded by the spread of MCR-1 plasmid-mediated resistance to polymyxins, at least in E. coli.