LE3 .A278 2021

2021

Coombs, Melanie
Hilchie, Ashley

Acadia University

Bachelor of Science

Honours

Biology

Biology

The emergence of multi-drug resistant pathogens and malignancies such as cancer has presented an obstacle to treatment. These emerging issues warrant the development of novel therapies against human malignancies. Another concern is the decrease in amphibian populations worldwide and damage to the aquaculture industry caused by amphibian and fish pathogens, respectively. Antimicrobial peptides (AMPs) are promising candidates as novel treatments for conditions in both humans, fish, and frogs. AMPs are very small proteins that are widespread throughout organisms and play a role in innate immunity. The natural role and clinical potential of AMPs magainin and pleurocidin were reviewed. Magainin is an AMP isolated from the African clawed frog (Xenopus laevis). There is a significant body of research on this peptide as the AMP was one of the first to be isolated from organisms. This analysis found particular potential for magainin as a novel therapy against amphibian fungal pathogens, human cancers, and Gram-negative species of bacteria. Pleurocidin is an AMP isolated from the winter flounder (Pseudopleuronectes americanus). This peptide is slightly larger than magainin and shows potential as a novel treatment against human cancers as well as bacterial Vibrio fish pathogens. Drawbacks to the use of these peptides as therapies include instability in vivo. Future investigations on these peptides should include studies on optimization strategies for the peptides to ensure low toxicity to normal cells while retaining high toxicity to target microbes. In addition to amphibian and fish AMPs, some human AMPs show potential as novel cancer therapies. This thesis includes an appendix on the human AMP hepcidin, which is synthesized in the liver. Hepcidin likely plays a role in innate anticancer immunity and actively kills human myeloma cells. With data from Dr. Coombs and colleagues , a draft of the published paper was written. The reviews on magainin, pleurocidin, and the hepcidin paper all demonstrate the significant potential for these AMPs as novel therapies and warrant further investigation.

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https://scholar.acadiau.ca/islandora/object/theses:3661