How many antimicrobial peptide molecules kill a bacterium? The case of PMAP-23

ACS Chem Biol. 2014 Sep 19;9(9):2003-7. doi: 10.1021/cb500426r. Epub 2014 Jul 30.

Abstract

Antimicrobial peptides (AMPs) kill bacteria mainly through the perturbation of their membranes and are promising compounds to fight drug resistance. Models of the mechanism of AMPs-induced membrane perturbation were developed based on experiments in liposomes, but their relevance for bacterial killing is debated. We determined the association of an analogue of the AMP PMAP-23 to Escherichia coli cells, under the same experimental conditions used to measure bactericidal activity. Killing took place only when bound peptides completely saturated bacterial membranes (10(6)-10(7) bound peptides per cell), indicating that the "carpet" model for the perturbation of artificial bilayers is representative of what happens in real bacteria. This finding supports the view that, at least for this peptide, a microbicidal mechanism is possible in vivo only at micromolar total peptide concentrations. We also showed that, notwithstanding their simplicity, liposomes represent a reliable model to characterize AMPs partition in bacterial membranes.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / metabolism*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Drug Evaluation, Preclinical / methods*
  • Escherichia coli / drug effects*
  • Lipids / chemistry
  • Liposomes / metabolism
  • Microbial Sensitivity Tests
  • Molecular Sequence Data

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Lipids
  • Liposomes
  • porcine myeloid antibacterial peptide 23