Peptide‐based antibiotics: A potential answer to raging antimicrobial resistance

Abstract

Antibiotic resistance is an increasing problem worldwide. The emergence and spread of multidrug-resistant bacteria leads to treatment failure and is associated with severe outcomes: increased mortality, morbidity, and expenditure. For some of these organisms, no treatment option is available. In contrast, very few new antibiotics are currently being developed and no new classes of antibiotics which are active against Gram-negative bacilli are under investigation. During the past decade, several peptide-based antimicrobials of vertebrate origin were identified as a novel and promising class of antibiotics. Peptide-based antibiotics are attractive both to fundamental research (a novel mechanism of action) and for their potential therapeutic applications. They are relatively small molecules, their action is fast and lethal to a large spectrum of pathogens, and they seem to escape many of the drug resistance mechanisms. Compared to classical antibiotics, peptides portray a highly modular synthetic antimicrobial system. As shown for the frog peptides, dermaseptins, this system allows a multitude of simple and cost-effective chemical modifications that dramatically affect activity in terms of potency and selectivity. Unlike classical antibiotics that must penetrate the target cell to act on it, antimicrobial peptides are believed to kill target cells by destroying their membrane(s). Theoretically, this mode of action should severely reduce microbial resistance and represents, therefore, a promising alternative in the treatment of raging multidrug-resistant infectious diseases. Drug Dev. Res. 50:440–447, 2000. © 2000 Wiley-Liss, Inc.