Experimental evolution of resistance to an antimicrobial peptide

Proc Biol Sci. 2006 Jan 22;273(1583):251-6. doi: 10.1098/rspb.2005.3301.

Abstract

A novel class of antibiotics based on the antimicrobial properties of immune peptides of multicellular organisms is attracting increasing interest as a major weapon against resistant microbes. It has been claimed that cationic antimicrobial peptides exploit fundamental features of the bacterial cell so that resistance is much less likely to evolve than in the case of conventional antibiotics. Population models of the evolutionary genetics of resistance have cast doubt on this claim. We document the experimental evolution of resistance to a cationic antimicrobial peptide through continued selection in the laboratory. In this selection experiment, 22/24 lineages of Escherichia coli and Pseudomonas fluorescens independently evolved heritable mechanisms of resistance to pexiganan, an analogue of magainin, when propagated in medium supplemented with this antimicrobial peptide for 600-700 generations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Directed Molecular Evolution*
  • Drug Resistance, Bacterial*
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Pseudomonas fluorescens / drug effects*
  • Pseudomonas fluorescens / genetics

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • pexiganan