This project explores the ability of various compounds to inhibit variants of the New Delhi Metallo-Beta-Lactamase (NDM) enzyme. Metallo-beta-lactamases (MBLs) are enzymatic resistance mechanisms expressed by a growing number of bacteria found to exhibit antibiotic resistance. While other resistance mechanisms can be treated, no clinically-viable inhibitor exists for MBL enzymes. Due to this looming threat, significant effort has been put into identifying such a drug in recent years and this project contributes to those efforts. We performed minimum inhibitory concentration (MIC) assays that determine the lowest drug concentration necessary to stop growth of bacteria. They consist of series of agar plates into which a concentration gradient of antibiotics has been infused. The first round of assays confirms the MIC value of the wild-type MBL in the presence of the antibiotic meropenem. The second round of assays includes the addition of a potential inhibitor and can reveal its effect on the growth of NDM-expressing bacterial populations when used in conjunction with meropenem. We are searching for an inhibitor that exhibits different effects on growth between variants of the same enzyme. Early trials indicate that the NDM-10 variant may respond differently to captopril (with meropenem) compared to other NDM variants. Future studies would further explore this outlier variant as well as investigate other potential inhibitors identified in by collaborators or our own lab. All three undergraduates working on this project intend to attend medical school and incorporate research into our careers in various ways. This project not only allows us to design and conduct our own scientific inquiry but also allows us to investigate a clinically-relevant research topic.
Authors: Aidan Sturgill, Alex Szymczak, Zac Green
Advisor: Michael Crowder, Chemistry and Biochemistry
Graduate Advisor: Zishuo Cheng, Chemistry and Biochemistry
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