Evaluation of Novel Antimicrobial Peptides as Topical Anti-Infectives with Broad-Spectrum Activity against Combat-Related Bacterial and Fungal Wound Infections
Abstract
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 are thus less likely to develop resistance to AMPs. Riptide Bioscience has synthesized thirty-one novel dAMPs in four iterative rounds. The dAMPs were evaluated for their antimicrobial potency against 11 strains of gram positive and gram negative bacteria and 7 strains of fungi. Standard MIC (Minimum Inhibitory Concentration) assays were conducted according to CLSI guidelines. Cytotoxicity was determined using L929 fibroblasts into which the luciferase gene had been transfected. Time-kill assays used P. aeruginosa (Xen5) and S. aureus (Xen36) cultures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1048281
Entities
People
- Louis E. Clemens