Date of Award
Chemistry and Biochemistry
Gregory Wiedman, Ph.D.
Wyatt Murphy, Ph.D.
Cecilia Marzabadi, Ph.D.
Fr. Gerald Buonopane, Ph.D.
flippase inhibitor, drug synergy, drug resistance, drug target, antimicrobial peptide, antifungal peptide
Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the nanoparticles formed by the drug in solution are a likely contributor to the ability for various versions of the peptide to work synergistically when mixed in checkerboard assays. Chapter 3 details the investigation of a P4 type ATPase flippase inhibitor as an antimicrobial agent against C. neoformans and to potentiate the effects of Caspofungin. Efficacy of the peptide was observed in vitro against the wild type strain. Annexin assays and confocal microscopy provide evidence towards the underlying mechanism of activity, relating to phosphatidylserine distribution in the membrane. Flippase inhibitors are drugs ripe for investigation due to their antimicrobial potential against drug resistant microbes.
Tancer, Robert, "Flippase Inhibitors as Antimicrobial Agents" (2022). Seton Hall University Dissertations and Theses (ETDs). 2981.
copyright release, Humimycins
04-25-2022-M-spectrum-AFP.pdf (745 kB)
copyright release, AFP
ATP-11C-copy-right.docx (3058 kB)
copyright release, ATP11C-Cdc50a