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Mycobacterium tuberculosis  ( Mtb)  mutants lacking  rv1411c , which encodes the lipoprotein LprG, and  rv1410c , which encodes a putative efflux pump, are dramatically attenuated for growth in mice. Here we show that loss of LprG-Rv1410 in  Mtb  leads to intracellular triacylglyceride (TAG) accumulation, and overexpression of the locus increases the levels of TAG in the culture medium, demonstrating a role of this locus in TAG transport. LprG binds TAG within a large hydrophobic cleft and is sufficient to transfer TAG from donor to acceptor membranes. Further, LprG-Rv1410 is critical for broadly regulating bacterial growth and metabolism  in vitro  during carbon restriction and  in vivo  during infection of mice. The growth defect in mice is due to disrupted bacterial metabolism and occurs independently of key immune regulators. The  in vivo  essentiality of this locus suggests that this export system and other regulators of metabolism should be considered as targets for novel therapeutics.

Mycobacterial Metabolic Syndrome: LprG and Rv1410 Regulate Triacylglyceride Levels, Growth Rate and Virulence in Mycobacterium tuberculosis