Experimental evolution of resistance to an antimicrobial peptide.
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.
Department of Biology, McGill University, 1205 Avenue Dr Penfield, Montreal, Que H3A 1B1, Canada.
Gabriel G
GG
Perron
Michael
M
Zasloff
Graham
G
Bell
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D019020:Directed Molecular Evolution; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D011551:Pseudomonas fluorescens / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C093828:pexiganan