Abstract

The twentieth century antibiotic armamentarium included a number of peptide-based compounds, mostly produced by spore-forming microorganisms. Characteristically, these peptide antibiotics are synthesized by multienzymatic complexes and display complicated molecular structures. Peptide antibiotics, however, were seldom the drugs of choice for systemic therapy because of toxicities. At the dawn of the twenty-first century, the use of peptide-based antibiotics is envisioned anew with more optimism, due to the discovery of a novel class of ribosome derived antimicrobial peptides that display promising properties. Animal-derived antimicrobial peptides are believed to kill target cells by disrupting their membrane(s). Compared with conventional antibiotics this peptide-based antimicrobial system represents several advantages: (1) antimicrobial peptides seem to escape most known drug resistance mechanisms; (2) they have a large spectrum of potential targets with rapid cidal activity toward bacteria, protozoa, yeast, fungi, enveloped viruses, and cancer cells; (3) they portray a highly modulable antimicrobial system since peptide chemistry allows a multitude of simple, rapid and cost-effective chemical modifications. In addition to their membrane disrupting activity, antimicrobial peptides are reportedly able to—directly as well as indirectly - modulate responses of the innate immune system. Such antimicrobial system is attracting increasing interest for a variety of potential biomedical applications, including its use in therapeutics and as a food preservative. A few antimicrobial peptides are presently being evaluated in various stages of clinical trials, mostly for topical applications. In the future, however, the deplorable situation of ever increasing multidrug resistance and the lack of available alternatives may reveal strong enough arguments to stimulate the development of strategies that will allow the safe systemic administration of such peptides and put to advantage their incontestable advantageous properties.