title: Antimicrobial Peptides: Mechanisms of Action and Resistance.
abstract: More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide's structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.
authors.affiliation: 1 University of Strasbourg/CNRS, Chemistry Institute, Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Bechinger
authors.affiliation: 2 University of Minnesota School of Dentistry, Minneapolis, MN, USA.
authors.forename: S-U
authors.initials: SU
authors.lastname: Gorr
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D016905:Gram-Negative Bacterial Infections / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins
keywords: antibacterial agents; antibiotic resistance bacterial; cell membrane; cell wall; gram negative bacteria; gram positive bacteria