Antimicrobial peptides: broad-spectrum antibiotics from nature.

No therapeutically useful new classes of antibiotics have been identified in the past quarter of a century This has become of major consequence in the face of the increase in the incidence of significant antibiotic resistance in the past decade. Indeed, strains of several important pathogens have been identified for which very few, or even no, possibilities for antibiotic therapy exist. Although several broad-spectrum improved variants of existing antibiotic classes have been produced (e.g. new fluoroquinolones, imipenem), it seems that bacteria can relatively easily become resistant to these by modulation of known resistance mechanisms. For this reason there is great interest in identifying novel antibiotic classes with potential in human therapeutics. Human beings and other species are continually exposed to numerous bacteria. Even in the absence of an immune response, they rarely become infected because of the potency of their so-called non-specific defenses. Thus, it is worth looking to these defenses as a potential source of new antimicrobial strategies. In the past decade it has become apparent that many organisms use cationic peptides as a major non-specific defense against infections (Table 1). Indeed, more than 140 cationic peptides are known, having been identified in nearly every species of life [l]. In plants (e.g. thionins) and insects (e.g. cecropins and insect defensins), cationic peptides provide the predominant mechanism of defense against bacteria and fungi. In insects, such peptides are inducible by mechanisms that