| Structural highlights
Function
[LPRG_MYCTU] TLR2 agonist that can inhibit primary human macrophage MHC-II Ag processing. Required for Rv1410c (P55) activity.[1] [2]
Publication Abstract from PubMed
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.,Martinot AJ, Farrow M, Bai L, Layre E, Cheng TY, Tsai JH, Iqbal J, Annand JW, Sullivan ZA, Hussain MM, Sacchettini J, Moody DB, Seeliger JC, Rubin EJ PLoS Pathog. 2016 Jan 11;12(1):e1005351. doi: 10.1371/journal.ppat.1005351., eCollection 2016 Jan. PMID:26751071[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gehring AJ, Dobos KM, Belisle JT, Harding CV, Boom WH. Mycobacterium tuberculosis LprG (Rv1411c): a novel TLR-2 ligand that inhibits human macrophage class II MHC antigen processing. J Immunol. 2004 Aug 15;173(4):2660-8. PMID:15294983
- ↑ Farrow MF, Rubin EJ. Function of a mycobacterial major facilitator superfamily pump requires a membrane-associated lipoprotein. J Bacteriol. 2008 Mar;190(5):1783-91. Epub 2007 Dec 21. PMID:18156250 doi:10.1128/JB.01046-07
- ↑ Martinot AJ, Farrow M, Bai L, Layre E, Cheng TY, Tsai JH, Iqbal J, Annand JW, Sullivan ZA, Hussain MM, Sacchettini J, Moody DB, Seeliger JC, Rubin EJ. Mycobacterial Metabolic Syndrome: LprG and Rv1410 Regulate Triacylglyceride Levels, Growth Rate and Virulence in Mycobacterium tuberculosis. PLoS Pathog. 2016 Jan 11;12(1):e1005351. doi: 10.1371/journal.ppat.1005351., eCollection 2016 Jan. PMID:26751071 doi:https://dx.doi.org/10.1371/journal.ppat.1005351
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