Antimicrobial Peptides as Therapeutic Agents

Copyright © 2012 Mathew Upton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In developing this special issue, we sought to raise awareness of the potential of antimicrobial peptides (AMPs) for clinical use and to highlight recent developments in the field. The issue contains research articles covering the full spectrum of contemporary work, ranging from the rational design of synthetic peptides and discovery of bacteriocins, to testing of the efficacy of AMPs in animal models. We have included two expert reviews reflecting on the potential of both eukaryotic and prokaryotic peptide antibiotics for clinical use. The antibiotic development pipeline is devoid of imminent solutions to the problems caused by resistant gram-negative bacteria and only a small number of new agents exist for therapy of infections caused by gram-positives. The pathway for development of new antibiotics is both long and extremely expensive and, therefore, " big-pharma " has not invested significantly in this area for decades. The scarcity of antibiotics to combat infectious disease is commonly acknowledged and the specter of untreat-able infections has been widely publicized. However, some additional potential impacts of the absence of efficacious antibiotics are not as widely discussed. The inability to reliably treat infections could potentially mean that all elective surgery ceases, and, moreover, there could be significant restrictions placed on the use of cancer chemotherapy. Thus, in order to maintain anything like the level of medical care that many of us now enjoy, we must devote considerable effort to find solutions to this steadily-evolving clinical dilemma. AMPs appear to merit a prominent position in the catalogue of pharmaceuticals that should be more exhaustively investigated in our search for new antimicrobial agents. Many AMPs have potent activity against bacteria, including those that are resistant to conventional antibiotics. Their activity is often relatively-specifically directed against certain genera or groups of bacteria, which could limit damaging effects on a patient's commensal flora. AMPs generally exhibit high stability to wide ranges in pH and temperature, characteristics that may be beneficial for their scaled-up production and formulation into deliverable products. Also, due to their rather specific modes of action, many AMPs exhibit low toxicity for eukaryotic cells, providing an opportunity for a wide therapeutic window. Their typical mode of action is also linked to a low …