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

Martinot, Amanda J.; Farrow, Mary; Bai, Lu; Layre, Emilie; Cheng, Tan-Yun; Tsai, Jennifer H.; Iqbal, Jahangir; Annand, John W.; Sullivan, Zuri A.; Hussain, M. Mahmood; Sacchettini, James; Moody, D. Branch; Seeliger, Jessica C.; Rubin, Eric J.; Boshoff, Helena Ingrid

doi:10.1371/journal.ppat.1005351

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

Journal Article · Mon Jan 11 00:00:00 EST 2016 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1005351· OSTI ID:1252767

Martinot, Amanda J. ^[1]; Farrow, Mary ^[1]; Bai, Lu ^[2]; Layre, Emilie ^[3]; Cheng, Tan-Yun ^[3]; Tsai, Jennifer H. ^[4]; Iqbal, Jahangir ^[5]; Annand, John W. ^[3]; Sullivan, Zuri A. ^[3]; Hussain, M. Mahmood ^[5]; Sacchettini, James ^[4]; Moody, D. Branch ^[1]; Seeliger, Jessica C. ^[2]; Rubin, Eric J. ^[1]; Boshoff, Helena Ingrid ^[6]

Harvard School of Public Health, Boston, MA (United States)
Stony Brook Univ., NY (United States)
Harvard Medical School, Boston, MA (United States)
Texas A & M Univ., College Station, TX (United States)
SUNY Downstate Medical Center, Brooklyn, NY (United States)
National Inst. of Health (NIH), Bethesda, MD (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: SUNY Health Now Network of Excellence

Grant/Contract Number:: U19 AI076217; R01 049313; P01 AI074805

OSTI ID:: 1252767

Journal Information:: PLoS Pathogens, Vol. 12, Issue 1; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 64 works

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

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