Abstract
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.
Highlights
Tuberculosis continues to be a major global health threat
Of the estimated 2 billion people worldwide currently infected with Mycobacterium tuberculosis (Mtb), surprisingly few go on to develop active tuberculosis (TB) disease
LprG and Rv1410 Regulate Triacylglyceride Levels and Virulence in Mtb environment likely play an important role in this process
Summary
Tuberculosis continues to be a major global health threat. Mycobacterium tuberculosis (Mtb) is estimated to infect 2 billion people worldwide, or one-third of the world’s population [1]. Mtb is able to survive during periods of reduced growth and has the capacity to regrow rapidly. Unlike other known mycobacterial lipoproteins, LprG is in an operon with a putative integral membrane transporter, Rv1410, a member of the major facilitator superfamily (MFS) [10,11]. Both genes are required in M. smegmatis for normal cell wall composition and for efflux of toxins such as ethidium bromide [12]. LprG and Rv1410 might function together to position mycobacterial lipids in the cell wall
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