The rapid increase of antibiotic resistance presents a serious problem in traditional, small-molecule based therapies. Antimicrobial peptides provide an attractive alternative that targets the bacterial cell membrane. Cathelicidins are a family of small, cationic, antimicrobial peptides found in humans and other species as a part of the innate immune system. A Trp-rich peptide sequence derived from water buffalo (Bubalus bubalis), buCATHL4B, displayed potent antimicrobial activity. In this work, Trp residues in the sequence were replaced with other aromatic amino acids. Minimal inhibitory concentration (MIC) results demonstrated activity against E.coli (EC), S.aureus (SA), P.aeruginosa (PA), A.baumannii (AB). Lipid vesicle leakage and E.coli inner and outer membrane leakage assays were performed to further understand the permeabilization activity of the peptides. Lipid vesicle binding and quenching experiments were also performed to gain an understanding of how the peptides interacted with lipid bilayers. Initial MIC results indicate the original, tryptophan-rich sequence, and the phenylalanine substituted sequences having strong inhibition of bacterial growth. In permeabilization assays, peptides with phenylalanine substitutions have higher levels of membrane permeabilization than those substituted with tyrosine. In addition, one of the two-tyrosine substituted sequence, YWY, behaves most differently in the lowest antimicrobial activity, showing no permeabilization of bacterial membranes. Ongoing experiments are focusing on the peptide orientation in bilayers and the secondary structure of the peptides when in solution and bound to bilayers.

Investigating the role of aromatic amino acids in the Trp-rich antimicrobial peptide buCATHL4B

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.