Microbiology and Immunology Graduate Program
BVS – Madras Veterinary College, Tanuvas, Chennai
MVS – Veterinary Parasitology I.V.R.I., Bareilly

Email: sm452@drexel.edu

Advisor: Dr. Akhil Vaidya
 
Thesis Research Summary

Malaria is reemerging as perhaps the biggest infectious killer. Three to five hundred million people are infected annually, and approximately 2–3 million people die of malaria every year, which includes one child every 30 seconds. With resistance to antimalarial drugs on the rise, new treatments are badly needed. Parasite mitochondrial functions are potential targets for antimalarial drugs, either in use or in development. The main focus within the laboratory is the elucidation of the mitochondrial physiology and mechanisms of action and resistance to drugs that target the parasite’s mitochondrion. Earlier studies provided insights into the mode of action for atovaquone, which inhibits ubiquinol-cytochrome c oxidoreductase, an enzyme complex of the electron transport chain (ETC) in the parasite’s mitochondrial inner membrane, and into the synergistic effect of proguanil with atovaquone. We recently found that in culture Plasmodium falciparum, the most lethal human malaria parasite species, can survive 48 hours of exposure to atovaquone and are continuing to investigate how the parasites develop resistance to this drug. Our recent findings suggest that the ETC, which is blocked by atovaquone, is not necessary for energy production in the parasites. The importance of the ETC rather lies in pyrimidine biosynthesis, at least in the erythrocytic stages. Currently, I am involved in a project that includes expression of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase in the rodent malaria parasite P. berghei. Additionally, I plan to study the dynamics of parasite clearance and death in atovaquone-treated mice.