One‐third of the world's population is infected by Mycobacterium tuberculosis (M.tb). Two million people die each year from tuberculosis (TB), the disease caused by this bacterium. TB primarily affects the lungs and is easily transmitted. One way to kill M. tb might be to inhibit the enzyme dihydrofolate reductase (DHFR). DHFR catalyzes the production of tetrahydrofolate by transferring a hydrogen ion (H−) from NADPH to dihydrofolate, thereby releasing tetrahydrofolate and NADP+. Tetrahydrofolate is essential to the bacteria's survival, and is a cofactor that is needed for the synthesis of the DNA base thymine. Isoniazid is one antibiotic already used to treat TB by targeting several TB proteins that are necessary for building M. tb cell walls and inhibiting DHFR. Unfortunately, strains of M. tb are evolving resistance to isoniazid, so next generation antibiotics are needed. A variation of isoniazid could be designed to avoid resistance, and to inhibit DHFR, thereby targeting bacterial DNA synthesis. The Valders SMART Team (Students Modeling A Research Topic), using 3D printing technology, created a physical model of DHFR and a possible inhibitor of tetrahydrofolate production. Supported by a grant from NIH‐NCRR‐SEPA.
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