Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides

Cationic antimicrobial peptides (CAMPs) are integral compounds of the antimicrobial arsenals in virtually all kinds of organisms, with important roles in microbial ecology and higher organisms' host defense. Many bacteria have developed countermeasures to limit the efficacy of CAMPs such as defensins, cathelicidins, kinocidins, or bacteriocins. The best-studied bacterial CAMP resistance mechanisms involve electrostatic repulsion of CAMPs by modification of cell envelope molecules, proteolytic cleavage of CAMPs, production of CAMP-trapping proteins, or extrusion of CAMPs by energy-dependent efflux pumps. The repertoire of CAMPs produced by a given host organism and the efficiency of microbial CAMP resistance mechanisms appear to be crucial in host-pathogen interactions, governing the composition of commensal microbial communities and the virulence of bacterial pathogens. However, all CAMP resistance mechanisms have limitations and bacteria have never succeeded in becoming fully insensitive to a broad range of CAMPs. CAMPs or conserved CAMP resistance factors are discussed as new mediators and targets, respectively, of novel and sustainable anti-infective strategies.