UCLA

Infections due to antibiotic-resistant bacteria cause tens of thousands of deaths yearly and pose a significant economic and social burden. The need for new classes of antimicrobial drugs is exigent as microbes continue to gain resistance to even the newest and more effective antibiotics. In this thesis, I present the results of a high-throughput screening (HTS) effort to identify small-molecule inhibitors of the Sortase A (SrtA) enzyme. SrtA is a promising drug target that is responsible for decorating the peptidoglycan of Gram-positive bacteria with virulence factors. The newly developed cell-based assay employs the oral bacterium Actinomyces oris and was used to interrogate a chemical library of over 200,000 compounds. SrtA inhibitors discovered by HTS are currently being analyzed using secondary assays. A new Bacillus subtilis strain has also been created that may be useful in HTS for compounds that inhibit the Staphylococcus aureus TarA enzyme. TarA is a N-Acetylmannosamine transferase that catalyzes the first committed step in wall teichoic acid (WTA) biosynthesis. Inhibitors discovered using this new strain could have useful anti-infective properties.