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Komodo-Dragon Inspired Cathelcidin Peptides Are Antibacterial Against Carbapenem-Resistant Klebsiella pneuonmiae

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dc.contributor.advisor van Hoek, Monique Hitt, Christopher
dc.creator Hitt, Christopher 2020-05-29 2021-09-22T00:06:02Z 2022-05-30T06:58:22Z
dc.description This thesis has been embargoed for 2 years. It will not be available until May 2022 at the earliest. en_US
dc.description.abstract The rise of carbapenem-resistant enterobacteriaceae (CRE) is a growing crisis that requires development of novel therapeutics. To this end, cationic antimicrobial peptides (CAMPs) represent a potential source of new potential therapeutics to treat difficult pathogens such as Klebsiella pneumoniae (CRKP), which has gained resistance to many if not all currently approved antibiotics making treatment difficult. In this paper we examined the anti-CRKP antimicrobial activity of the predicted cathelicidins derived from Varanus komodoensis (Komodo dragon) as well as synthetic antimicrobial peptides that we created. We did not observe significant anti-CRKP activity of for the predicted native Komodo cathelicidin peptides. We found significant antimicrobial activity of that the novel peptides DRGN-6, -7 and -8 were antimicrobial against CRKP with MICs between 4-8 μg/mL. DRGN-6 peptide was the most effective peptide against CRKP. We characterized the abilities of these peptides to disrupt the hyperpolarization of the bacterial membrane as well as their ability to form pores in the membrane. After further testing, these peptides showed higher than desired levels of hemolysis although in vivo testing in the waxworm Galleria mellonella showed no mortality associated with treatment by the peptide; however, CRKP-infected waxworms treated with peptide did not show an improvement in survival. Given the challenges of treating CRKP, identification of peptides with activity against it represents a promising avenue for further research. Given DRGN-6’s similar level of activity to colistin, DRGN-6 is a promising template for the development of novel antimicrobial peptide-based therapeutics. en_US
dc.language.iso en en_US
dc.subject chimeric peptides en_US
dc.subject ESKAPE pathogens en_US
dc.subject cationic antimicrobial peptides en_US
dc.subject novel antimicrobials en_US
dc.subject cathelicidins en_US
dc.subject carbapenem resistant Klebsiella pneumoniae en_US
dc.title Komodo-Dragon Inspired Cathelcidin Peptides Are Antibacterial Against Carbapenem-Resistant Klebsiella pneuonmiae en_US
dc.type Thesis en_US Master of Science in Biology en_US Master's en_US Biology en_US George Mason University en_US

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