Theses and Dissertations

Date of Award

5-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology

First Advisor

Dr. Yonghong Zhang

Second Advisor

Dr. Xiaoqian Fang

Third Advisor

Dr. Arnulfo Mar

Abstract

Pseudomonas aeruginosa is a Gram-negative, multidrug resistant bacterium that has been recognized as the prominent cause of nosocomial infections. Untreated acute and chronic infections associated with P. aeruginosa can develop into other diseases such as pneumonia, otitis externa, and osteomyelitis. P. aeruginosa infections commonly affect immunocompromised individuals such as cystic fibrosis, cancer, and burn patients. The misuse and overuse of antibiotics has contributed to the increased antibiotic resistance in P. aeruginosa and thus has led to an unmet need for discovery of novel antibiotic candidates. Protein biosynthesis is an essential metabolic process occurring in all bacteria and a validated target of many antibiotics currently used today. Interactions between translation initiation factor 1 (IF1) of P. aeruginosa and the 30S ribosomal subunit, required for the initiation and completion of protein synthesis, was previously investigated via NMR to reveal a full-length structure of IFI. NMR titration of an IF1-bound 30S complex revealed a short α-helix in IF1 was critical for ribosomal binding and function. Derived from this α-helix, a peptide was designed and tested against a series of Gram-negative and Gram-positive bacteria to assess its broad-spectrum antimicrobial properties. A high ability to inhibit bacterial growth was displayed against P. aeruginosa (MIC: 47 mg/ml), providing an insight to a novel target for antimicrobial development.

Comments

Copyright 2022 Nicolette Valdez. All Rights Reserved.

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