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

J Dobias1, L Poirel2, P Nordmann3

  • 1Emerging 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.

Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases
|March 28, 2017
PubMed
Abstract

Insights

Acquired resistance to cationic antimicrobial peptides (CAMPs) does not co-select for polymyxin resistance in bacteria. The spread of MCR-1 polymyxin resistance is unlikely to impede the therapeutic development of human CAMPs.

Area of Science:

  • Microbiology
  • Immunology
  • Drug Resistance

Background:

  • Cationic antimicrobial peptides (CAMPs) are crucial components of the human immune system.
  • Polymyxins are antibiotics that share a similar mechanism of action with CAMPs.
  • The emergence of MCR-1-mediated resistance to polymyxins poses a significant threat to public health.

Purpose of the Study:

  • To investigate whether resistance to CAMPs can lead to co-resistance to polymyxins.
  • To evaluate the impact of MCR-1, a plasmid-encoded polymyxin resistance determinant, on bacterial susceptibility to CAMPs.
  • To assess the potential implications for the therapeutic development of CAMPs.

Main Methods:

  • In vitro susceptibility studies were conducted.
  • Human CAMPs (cathelicidin LL-37, α-defensin 5, β-defensin 3) were tested.
  • MCR-1-producing and colistin-resistant Escherichia coli and Klebsiella pneumoniae strains were utilized.

Main Results:

  • No cross-resistance between CAMPs and colistin was observed in MCR-1-producing or chromosomally resistant E. coli and K. pneumoniae.
  • The presence of MCR-1 did not confer resistance to human CAMPs.
  • Bacterial resistance mechanisms to polymyxins did not affect susceptibility to CAMPs.

Conclusions:

  • The spread of MCR-1 plasmid-mediated resistance to polymyxins is unlikely to hinder the future therapeutic development of human CAMPs.
  • E. coli strains carrying MCR-1 remain susceptible to human CAMPs.
  • CAMPs represent a promising therapeutic avenue, unaffected by current polymyxin resistance.
Keywords:
EnterobacteriaceaeEscherichia coliKlebsiella pneumoniaeMCR-1colistindefensins

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