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

OBJECTIVES: 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.

METHODS: 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.

RESULTS: Cross-resistance to CAMPs and colistin mediated by MCR-1 or chromosomal mechanisms was neither observed in E. coli nor in K. pneumoniae.

CONCLUSION: 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.