Date of Award
Master of Science (MS)
Biochemistry and Molecular Biology
Dr. Yonghong Zhang
Dr. Xiaoqian Fang
Dr. Arnulfo Mar
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.
Valdez, Nicolette, "Structures and Regulations of Translation Initiation Factors in Pseudomonas aeruginosa Protein Biosynthesis to Develop New Potential Antimicrobial Agents" (2022). Theses and Dissertations - UTRGV. 1108.