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PLoS Pathog. 2016 Jan 11;12(1):e1005351. doi: 10.1371/journal.ppat.1005351. eCollection 2016 Jan.

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

Author information

1
Division of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
2
Department of Chemistry, Stony Brook University, Stony Brook, New York, United States of America.
3
Department of Medicine, Division of Immunology and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
4
Department of Chemistry, Texas A&M University, College Station, Texas, United States of America.
5
Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
6
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.

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.

PMID:
26751071
PMCID:
PMC4709180
DOI:
10.1371/journal.ppat.1005351
[Indexed for MEDLINE]
Free PMC Article

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