Date of Award

Summer 7-20-2022

Track

Chemistry

Degree Type

Thesis

Degree Name

Master of Science in Chemical Sciences (MSCB)

Department

Chemistry

Committee Chair/First Advisor

Thomas Leeper

Committee Member

Melanie Griffin

Committee Member

Meredith Baker

Abstract

Pseudomonas aeruginosa (PA) is a Gram-negative bacterium, often found in cystic fibrosis (CF) patients and can lead to the decline of lung functioning and premature death in 80% of infected patients when microcolonies form within the mucin of the lung. Due to its major capacity for antibiotic resistance, an alternative strategy towards defending against the bacterial invasion of PA is by the antibacterial activity of our own innate immune system with use of elements such as lysozyme. Pseudomonas aeruginosa inhibitor of vertebrate lysozyme class 1 (Ivyp1) is a periplasmic protein produced by gram-negative bacteria that inhibits the enzymatic activity of lysozyme. Previous studies have shown that Ivyp1 knockout production did not affect the growth of PA in breast milk or human saliva, however, the role of Ivy knockouts should be explored in additional lysozyme-rich environments. The aim of this project is to identify the optimal conditions for an Artificial Sputum Medium (ASM) that can most closely resemble the environment of CF lung sputum, determine what role the components of the CF lung environment have on bacterial growth between wildtype and the Ivyp1 knockout, and then determining if the restoration of the Ivyp1 knockout has some significant difference in bacterial growth patterns in comparison, within these environments as well. We propose that in the presence of lysozyme in an ASM, the absence of Ivyp1 production will reduce or impair the growth of PA. Achieving these results holds the possibility of the creation of a new therapeutic approach that targets Ivyp1 to allow the destruction of PA bacteria in the lung environment of a patient with CF by immune-response activity.

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