Peptide array based discovery of synthetic antimicrobial peptides

ANTIMICROBIAL PEPTIDES AS A MEANS TO COMBAT ANTIBIOTIC RESISTANCE The rise of antibiotic resistance has emphasized the shortcomings in antibiotic drug development (Boucher et al., 2013). The move from biological based discovery methods to chemical approaches to identify candidates has left the antibiotic pipeline painfully dry (Lewis, 2013). The paucity of compounds that are effective against antibiotic resistant pathogens has led to great interest in antimicrobial peptides (AMPs) as potential solutions to the rise of resistant organisms (Hancock and Sahl, 2006; Fox, 2013). AMPs are short (5–50 amino acid) peptides that are produced by virtually all organisms as part of an innate immune system. There are 2,398 AMPs that have been reported (Antimicrobial Peptide Database—September 2013) and over 80% are cationic AMPs (CAMPs). Most positively charged AMPs interact with anionic bacterial membranes (Schmidtchen andMalmsten, 2013) which leads to a rapid breakdown in membrane function and subsequent cell death (Wimley, 2010). It is this mechanism of action that is of interest as it should be difficult for bacteria to develop resistance against lethal concentrations of CAMPs. However, many AMPs have poor druglike properties and questions remain about that their ultimate utility as antibiotics (Brogden and Brogden, 2011). Great strides have been made in improving the protease stability; pharmacokinetics and therapeutic profile of peptide drugs and these methods have been used to improve the drug-like properties of AMPs. Despite the significant developments that have been made to advance AMPs through the clinical pipeline there has yet to be an approved AMP therapeutic (Vila-Farres et al., 2012). Clearly there is an ongoing need for additional AMP candidates as a tool in the fight against antibiotic resistant bacteria.