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

Antibiotic resistance is an increasing problem worldwide. The emergence and spread of multidrug-resistant bacteria leads to treatment failure and is a ssociated with severe outcomes: increased mortality, morbidity, and expendi ture. For some of these organisms, no treatment option is available. In con trast, very few new antibiotics are currently being developed and no new cl asses of antibiotics which are active against Gram-negative bacilli are und er investigation. During the past decade, several peptide-based antimicrobi als of vertebrate origin were identified as a novel and promising class of antibiotics. Peptide-based antibiotics are attractive both to fundamental r esearch (a novel mechanism of action) and for their potential therapeutic a pplications. They are relatively small molecules, their action is fast and lethal to a large spectrum of pathogens, and they seem to escape many of th e drug resistance mechanisms. Compared to classical antibiotics, peptides p ortray a highly modular synthetic antimicrobial system. As shown for the fr og peptides, dermaseptins, this system allows a multitude of simple and cos t-effective chemical modifications that dramatically affect activity in ter ms of potency and selectivity. Unlike classical antibiotics that must penet rate the target cell to act on it, antimicrobial peptides are believed to k ill target cells by destroying their membrane(s). Theoretically, this mode of action should severely reduce microbial resistance and represents, there fore, a promising alternative in the treatment of raging multidrug-resistan t infectious diseases. (C) 2000 Wiley-Liss, Inc.