Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.
Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
Hancock
Robert E W
RE
Centre for Microbial Diseases and Immunity Research, Room 232, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4. bob@cmdr.ubc.ca
Sahl
Hans-Georg
HG
D000891:Anti-Infective Agents, Local / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015195:Drug Design
D000891:Anti-Infective Agents, Local; D023181:Antimicrobial Cationic Peptides