Goring, Andrew
Mentor: Dr. Robert Clubb, Dr. Joseph Loo
Bacterial pathogens display glycopolymers on their surface that are required to mount an infection. My research focuses around wall teichoic acid (WTA) biosynthesis and, more specifically, the TagA N-acetylmannosamine transferase enzyme which catalyzes the last committed step of metabolites into this pathway. Gram+ Methicillin-Resistant Staphylococcus aureus (MRSA) strains are resistant to β-lactam antibiotics and have a high mortality rate, thus posing a significant threat to public health. Interestingly, the WTA biosynthetic pathway has drawn considerable interest as an antibiotic target, as genetically eliminating WTA production in MRSA re-sensitizes it to β-lactam antibiotics and attenuates its virulence.
My research aims to target and gain a better understanding of the WTA pathway for the development of new antibiotics. The first step is implementing a new high-throughput screening strategy to specifically find an inhibitor for the S. aureus TagA enzyme. This screen benefits from the large and diverse compound library offered by UCLA’s Molecular Shared Screening Resource (MSSR). The second is to establish structure-activity-relationships (SARs) for lead compounds identified in the screen. Finally, we seek to use proteomics approaches to define protein factors that form the “WTA synthome” in S. aureus. Precious metabolites moving through the pathway may be coupled from one enzyme to the next to conserve cellular resources, forming a “WTA synthome”. With TagA being the gate-keeper enzyme, it is likely a key member of the synthome. Identifying key components could lead to new drug targets that work by disrupting the protein machinery used for WTA biosynthesis.
