Stabilized Antimicrobial Peptides to Combat Multidrug-Resistant Biofilm

Infections involving multidrug resistant organisms (MDROs) post a substantial threat to military populations. Critical barriers to progress in the treatment of wound infections are the need for therapeutics effective against MDROs and therapeutics effective against biofilms. The goal of this application is to further develop two novel engineered antimicrobial peptides (eCAPs) for treatment of MDROs. The scope of this application builds on prior work with planktonic bacteria to evaluate the efficacy of two eCAPs against organisms within biofilms. Each eCAP will also be evaluated for cytotoxicity to establish therapeutic windows for product formulation in the context of a wound treatment. A second major focus is to design a topical delivery vehicle that will ensure retention of activity in wound exudates and a robust product for storage in austere environments. The formulations will be tested within simulated wound environments and against biofilms including mixed species biofilms. Results will be used to select a lead peptide and will provide the foundation for defining formulation parameters for further product development including animal studies in Phase II. By preventing/treating devastating infections, success of this project is expected to have a significant and sustained impact on reducing morbidity and mortality of wounded soldiers.