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.
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We gratefully acknowledge financial support (to R.E.W.H.) for peptide research from the Advanced Food and Materials Network, the Canadian Institutes for Health Research (CIHR), from Genome BC and Genome Prairie for the Pathogenomics of Innate Immunity research program, and from the Foundation for the National Institutes of Health, USA, and CIHR through the Grand Challenges in Global Health Initiative, and (to H.G.S.) from the German Research Foundation (DFG, various projects), the European Community (two 5th and 6th framework projects) and the BONFOR research program of the University of Bonn. R.E.W.H. is the recipient of a Canada Research Chair.
R.E.W.H. is a scientific advisory board member of Helix Biomedix and minor shareholder of Migenix, Inc., which are developing antimicrobial peptides, and a scientific advisory board member of Inimex Pharmaceuticals, which is developing immunomodulatory peptides as human therapeutics.
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Hancock, R., Sahl, HG. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24, 1551–1557 (2006). https://doi.org/10.1038/nbt1267
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