Each year, in the United States alone, hundreds of millions of antibiotic prescriptions are written with the hopes of treating various bacterial infections. Unfortunately, this penchant for prescribing antibiotics has in part led to the emergence of numerous antibiotic-resistance mechanisms in bacteria. One strategy for combatting such emerging resistance involves not the generation of new antibiotics, but rather the synthesis of small molecule inhibitors which complement existing antibiotics through targeting of the antibiotic resistance pathways themselves. My laboratory has focused upon one such pathway, the bacillithiol-dependent inactivation of the antibiotic fosfomycin. Specifically, we have sought to develop inhibitors which target the production of this low-molecular-weight thiol itself. Key to inhibitor development has been a reliance upon the natural carbohydrate scaffold of our target enzyme’s (BshB) substrate as way to enhance interactions through substrate mimicry and later explore the importance of various interactions within the BshB active site. Furthermore, in addition to yielding several research-based advances, this project has also been successfully leveraged to impact the pedagogical side of my role at a teaching-focused PUI. Specifically, problems encountered by students during their synthetic efforts have been translated into troubleshooting experiments for a first-year student research course. Such experiments thus allow us to introduce fundamental laboratory techniques while also fostering the development of critical thinking skills within these aspiring chemists.

Carbohydrate-based inhibitors of bacillithiol biosynthesis: Research advances & pedagogical applications

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.