title: Mycobacterial Metabolic Syndrome: LprG and Rv1410 Regulate Triacylglyceride Levels, Growth Rate and Virulence in Mycobacterium tuberculosis.
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.
authors.affiliation: Division of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Martinot
authors.affiliation: Division of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Farrow
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Emilie
authors.initials: E
authors.lastname: Layre
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Tan-Yun
authors.initials: TY
authors.lastname: Cheng
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Tsai
authors.affiliation: Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
authors.forename: Jahangir
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Annand
authors.affiliation: Division of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Zuri A
authors.initials: ZA
authors.lastname: Sullivan
authors.affiliation: Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, Texas, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Sacchettini
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Seeliger
authors.affiliation: Division of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D008074:Lipoproteins / Q000378:metabolism; D013058:Mass Spectrometry; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000472:pathogenicity*; D014376:Tuberculosis / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; C425143:P55 protein, Mycobacterium