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Basic Biology and Pathogenesis of M. tuberculosis. A major focus of our research is to identify the protein secretion systems of M. tuberculosis and the roles that M. tuberculosis secreted proteins play in pathogenesis, particularly in enabling M. tuberculosis to survive within macrophages. We study a specialized secretion system, called the SecA2 system. The SecA2 system secretes the SapM phosphatase, which has a role in promoting M. tuberculosis survival in macrophages. SapM prevents M. tuberculosis from being delivered to degradative phagolysosomal compartments in the macrophage. Most recently we discovered a chaperone protein named SatS that protects SapM from degradation and assists in SapM secretion out of the bacteria. Our mechanistic studies are defining the pathway that SapM takes to be delivered into the macrophage environment in order to protect M. tuberculosis from destruction by macrophages. We are also studying M. tuberculosis transporter systems (Mce transporters) that import lipids and are required for pathogenesis. The knowledge gained from our studies has the potential to reveal new targets for tuberculosis drugs and to drive development of new treatment strategies for tuberculosis.
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Alan A. Schmalstig, Andrew Wiggins, Debbie Badillo,Katherine S. Wetzel,Graham F. Hatfull,Miriam Braunstein
MBIOno. 1 (2024): e0292423-e0292423
Pharmaceuticsno. 6 (2023)
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bioRxiv (Cold Spring Harbor Laboratory) (2023)
CLINICAL PHARMACOLOGY & THERAPEUTICSno. 6 (2021): 1443-1456
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