Targeting Tat Export in Mycobacteria (2014)

Undergraduates: Andrew Krusell, Ellen Perkowski

Faculty Advisor: Miriam Braunstein
Department: Biology

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The Tat pathway is one of two major protein export pathways found in mycobacteria, and is essential to the growth and viability of M. tuberculosis. By targeting the Tat pathway, a new drug could inhibit the virulence and fitness of M. tuberculosis. Previous work has shown that the Tat pathway is required for M. smegmatis growth, a model organism for M. tuberculosis, when using succinate as a carbon source. In order for the bacteria to use succinate as a carbon source, succinate must first be transported from the extracellular environment into the bacterial cytoplasm. The Dct system of carbon transport has been studied extensively and offers a starting location for targeting succinate transport. We hypothesized that the Dct family of proteins, specifically DctP1 and DctP2, would be responsible for succinate import in M. smegmatis, similar to what is seen in other bacteria. Additionally, we hypothesized that DctP1 and DctP2 would be exported through the Tat system, therefore, in the absence of Tat export M. smegmatis would be unable to import succinate. Through the SURF program I was able to make progress in determining which Tat exported proteins in M. smegmatis are responsible for the import of succinate. Results suggest that DctP1 and DctP2 are both transported through the Tat pathway, but are not responsible for succinate transport. The protein DctA, in the same family of proteins, provides the next best possibility for research into Tat export.