Date

2018

Department or Program

Chemistry

Primary Wellesley Thesis Advisor

Donald Elmore

Abstract

Due to the increasing public health concern of antibiotic resistant bacteria, antimicrobial peptides (AMPs) are a promising area of research for the development of new therapeutics. AMPs induce bacterial cell death in one of two ways: translocating into the cell and interfering with its nucleic acids or permeabilizing the cell membrane and inducing cell lysis. While a large amount of previous research has focused on AMPs in dilute buffers, this does not accurately reflect the physiological conditions where AMPs would be active as drugs. Blood plasma and the extracellular matrix contain large concentrations of macromolecules that can affect the AMP’s ability to interact with the bacterial cell membrane. This thesis compares the activity of magainin and BF2, two well-characterized AMPs with different mechanisms of action, in dilute buffer to activity when crowded with macromolecules. Membrane permeabilization for magainin was shown to decrease in the presence of crowding via the propidium iodide uptake assay. There was little effect of crowding on the permeabilization caused by buforin II, which generally leaves membranes intact in its mechanism of action. Initial tryptophan fluorescence experiments suggest that membrane affinity changes under crowded conditions. The results demonstrate the importance of developing appropriate experiments to consider the potential effects of macromolecular crowding on AMP activity.

Available for download on Tuesday, April 25, 2023

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