Bacterial Resistance to Host Defence Peptides

Currently, antimicrobial drug resistance is a global problem that threatens to precipitate a ‘Post-antibiotic era’ in which the ability of common infections and minor injuries to kill is a very real possibility. A potential solution to this problem is the development of host defence peptides, which are endogenous antibiotics that kill microbes via membranolytic action, based in part on the belief that microbes were unlikely to develop resistance to this action. However, the incidence of microbes exhibiting resistance to the action of host defence peptides is growing and an increasingly diverse spectrum of mechanisms is being reported to underpin this resistance. These mechanisms can be broadly categorized as those that either: destroy these peptides, such as through the production of bacterial proteases; intercept/shield these peptides, such as by the release of host cell proteoglycans by bacterial enzymes; or export these peptides, such as via the use of bacterial efflux pumps. Here we give an overview of these mechanisms, with a focus on recent developments in this area, and then discuss the potential of inhibitors of these resistance mechanisms to treat infections due to bacterial pathogens.