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Graduate Defense: Madison Rizzo

November 28 @ 9:00 am - 10:00 am MST

Thesis Information

Title: Using NMR Chemical Shift Perturbations to Map Interactions Between Acyl-Acyl Carrier Proteins and Acyl Homoserine Lactone Synthases

Program: Master of Science in Chemistry

Advisor: Dr. Lisa Warner, Chemistry and Biochemistry

Committee Members: Dr. Rajesh Nagarajan, Chemistry and Biochemistry, and Dr. Don Warner, Chemistry and Biochemistry

Abstract

A pandemic of antibiotic resistance is underway and affecting multiple industries, including veterinary, agricultural, and healthcare. High bacterial population density is a major form of defense for bacterial cells against drugs, contributes to antibiotic resistance, and is one of the requirements for the formation of biofilms. Quorum sensing is a form of cell-to-cell communication that both gram-negative and gram-positive bacteria use to account for density behavior. When the population density of bacteria reaches a certain level (a “quorum”), there is an observed coordinated shift in gene expression that leads to optimized growth or virulence. Acyl carrier proteins (ACP) and the enzyme acyl-homoserine lactones synthase (AHLS), which are the building blocks for the formation of quorum sensing molecules, acyl-homoserine lactone (AHL) molecules signal the regulation of some of these expressed genes. AHLs are chemical autoinducers used in quorum sensing. This project contributes to an effort to map interactions between ACP1 and RhlI from Pseudomonas aeruginosa, using nuclear magnetic resonance (NMR) spectroscopy to better predict drug target sites to inhibit the production of AHL molecules. Here, I present the chemical shift backbone assignments for ACP1 and the optimized expression and purification of ACP1 and RhlI.