Evaluation of Novel Antimicrobial Peptides as Topical Anti-Infectives with Broad-Spectrum Activity Against Combat-Related Bacterial and Fungal Wound Infections
[Technical Report, Annual Report]
Riptide Bioscience, Inc
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Ballistic wound infection has become the greatest threat to the life and recovery of the combat casualty who survives the immediate trauma of the insult. Multidrug resistance and generation of recalcitrant biofilm are major obstacles in treating wounds. Antimicrobial peptides AMPs, also known as host defense peptides, are evolutionarily highly conserved components of the innate immune system that provide the first line of defense against invading pathogens in all multicellular organisms. Designed antimicrobial peptides dAMPs are synthesized peptides that have been rationally designed based on sequences found in naturally occurring AMPs. dAMPs are amphipathic cationic peptides with the ability to kill microbes by disrupting their membrane function. This mode of action rapidly kills antibiotic resistant microbes, even in biofilm. Bacteria have never succeeded in developing resistance to a variety of AMPs. 1 Riptide Bioscience has developed a unique Time-Kill assay using bioluminescent bacteria. This assay demonstrates the time needed to eliminate microbes in vitro as well as insight into the bactericidal mechanism of action of test compounds. 2 In vitro MIC and MBC assays have demonstrated that S. aureus, P. aeruginosa, and several strains of fungi do not develop resistance after repeated passage with dAMPs, whereas strains resistant to the antibiotics gentamicin, clindamycin or fluconazole are killed by dAMPs. The dAMPs also kill bacteria and fungi in their biofilm. 3 Three dAMPs RP504, RP554 and RP557 were evaluated in a porcine burn wound model for their ability to stop polymicrobial infections. RP557 was the most effective peptide. 4 Three dAMPs were evaluated for antifungal activity in a rat model of vulvovaginal candidiasis. R557 was the most effective in eradicating the infection. 5 RP557 has very limited cytotoxic effects on eukaryotic cells. 6 RP557 is being advanced to IND enabling studies.
- Medicine and Medical Research