The Genetic Basis of Microbial Resistance to Antimicrobial Peptides

Small cationic peptides with antibiotic properties have been isolated from a diverse array of evolutionarily divergent organisms, including insects, amphibians, mammals, and plants. They contribute to the innate immunity of the host by fending off opportunistic (i.e., environmental) microorganisms. Moreover, antimicrobial peptides present a chemical barrier early in infection before the mammalian host induces the specific type of immune response constituted by antibodies and T cells (1 ,2 ). Microorganisms have coexisted with their animal hosts for millions of years and have, in turn, evolved strategies that enable them to avoid or withstand the various microbicidal activities of the host (3 ). For example, the mammalian pathogen Salmonella typhimurium has several genes that confer resistance to host defense peptides, presumably allowing it to successfully colonize host tissues that are rich in antimicrobial peptides. The demonstration that mutants of S. typhimurium that are hypersusceptible to the killing effects of host-defense peptides are attenuated for virulence in mice has established that resistance to small cationic peptides is a virulence property of Salmonella (4 ) and, potentially, of other enteric pathogens.