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


CONCLUSIONS
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.
Emerging Antibiotic Resistance, Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Fribourg, Switzerland; INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland.
J
J
Dobias
Emerging Antibiotic Resistance, Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Fribourg, Switzerland; INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland; Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Fribourg, Switzerland.
L
L
Poirel
Emerging Antibiotic Resistance, Medical and Molecular Microbiology Unit, Department of Medicine, University of Fribourg, Fribourg, Switzerland; INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland; Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), Fribourg, Switzerland; Institute for Microbiology, University of Lausanne and University Hospital Centre, Lausanne, Switzerland. Electronic address: patrice.nordmann@unifr.ch.
P
P
Nordmann
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics; D011113:Polymyxins / Q000494:pharmacology*
D023181:Antimicrobial Cationic Peptides; D029968:Escherichia coli Proteins; C000614037:MCR-1 protein, E coli; D011113:Polymyxins; D003091:Colistin
Enterobacteriaceae; Escherichia coli; Klebsiella pneumoniae; MCR-1; colistin; defensins