| The emergence of multi-drug resistant bacterial strains has caused numerous antibiotics to lose their utility. Current antibiotic agents block bacterial cell wall synthesis, protein or RNA synthesis, and DNA replication. However, bacterial strains have developed resistant to all of these agents and new antibiotic agents are needed to combat this growing problem. In the past two decades, antimicrobial peptides (APs) from higher organisms have been found to exhibit broad spectrum activity against a wide range of microorganisms including Gram-negative and Gram-positive bacteria, fungi, and viruses. APs have been viewed as a promising potential therapeutic, but they have their own disadvantages, including cytotoxicity, cost of production and lack of oral availability. Short synthetic peptides have been created to mimic antimicrobial peptides and multivalency has been used as a tool to collectively enhance avidity when compared to a monovalent peptide. My contributions to these efforts include: (i) comparing, screening and studying various APs and a multivalent analog for the ability to induce resistance; (ii) assessing the spectrum of activity of a promising multivalent AP, RW4D, under physiological conditions, both in vivo and in vitro ; and (iii) studying the mode of action of (RW)4D through analysis of its ability to stimulate hydroxyl radicals and bind DNA. These results give insights into the potential of APs to serve as anti-infective agents. |
