Renee Bouley, a fourth-year graduate student in the Department of Chemistry and Biochemistry, has received a Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship from the National Institutes of Health (NIH). The fellowship will provide two years of funding for Bouley’s project, “Discovery of a new class of antibacterials that inhibits penicillin-binding proteins.”
Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has developed a resistance to many commonly used antibiotics, such as penicillin and amoxicillin. MRSA has been identified by the Centers for Disease Control and Prevention as a serious threat to public health in the United States, which needs prompt action to keep MRSA infections in check. There are several FDA-approved antibiotics that are currently used to treat MRSA infections; however; some strains of MRSA are beginning to develop resistance to these drugs. The emergence of these highly virulent strains emphasizes the urgent need for new antibiotics.
Bouley’s research focuses on developing novel antibiotics that show excellent in vitro activity against both susceptible and MRSA strains. These compounds were discovered through computational docking and scoring to a low affinity penicillin-binding protein found in MRSA called PBP2a. Her goals are to synthesize a library of these antibiotics to develop a structure–activity relationship, evaluate the in vitro activity of the compounds against a panel of live bacteria, demonstrate binding to PBP2a and other penicillin-binding proteins, assess the toxicity and pharmacokinetic profile of active compounds, and improve upon the in vivo efficacy. Bouley is a former fellow of the Chemistry-Biochemistry-Biology Interface Program at Notre Dame and is advised by Shahriar Mobashery, Navari Family Professor of Life Sciences and Mayland Chang, research professor of chemistry and biochemistry.
“This is an interdisciplinary project that involves organic synthesis, biochemistry, microbiology, structural biology, pharmacology, and animal models of infection,” Bouley explained. “These studies will expand our knowledge in designing effective anti-MRSA compounds and understanding this new class of antibacterials.”
The NIH fellowship was named for Ruth L. Kirschstein, M.D., who a champion of research training and a strong advocate for the inclusion of underrepresented individuals in the scientific workforce. She is best known for her contributions to developing the polio vaccine and becoming the first female director of an NIH institute.