Lipoprotein LprG Binds Lipoarabinomannan and Determines Its Cell Envelope Localization to Control Phagolysosomal Fusion

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The causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), persists in phagosomes inside infected macrophages. Mtb expresses lipoarabinomannan (LAM), which inhibits fusion of phagosomes with lysosomes as a means for Mtb to evade host defense. LAM is present in the cell envelope, which surrounds Mtb and interfaces with the host, but its localization remains unclear. We show that LprG, an Mtb lipoprotein, binds LAM and controls its distribution in the cell envelope. A mutant strain of Mtb that lacks LprG has less LAM at the surface of the cell envelope. This decreases LAM-mediated inhibition of phagosome-lysosome fusion, thereby impairing an immune evasion mechanism. We propose that LprG facilitates transfer of LAM from the plasma membrane into the cell envelope, enhancing its interaction with the host and ability to regulate host defense. Our results reveal mechanisms that determine bacterial cell envelope function and influence host-pathogen interactions and pathogen evasion of host defense.

Vyšlo v časopise: Lipoprotein LprG Binds Lipoarabinomannan and Determines Its Cell Envelope Localization to Control Phagolysosomal Fusion. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004471
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004471

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1. KaurD, GuerinME, SkovierovaH, BrennanPJ, JacksonM (2009) Chapter 2: Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis. Adv Appl Microbiol 69 : 23–78.

2. BrikenV, PorcelliSA, BesraGS, KremerL (2004) Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Mol Microbiol 53 : 391–403.

3. BrennanPJ, NikaidoH (1995) The envelope of mycobacteria. Annu Rev Biochem 64 : 29–63.

4. TorrellesJB, SchlesingerLS (2010) Diversity in Mycobacterium tuberculosis mannosylated cell wall determinants impacts adaptation to the host. Tuberculosis (Edinb) 90 : 84–93.

5. ShinDM, YukJM, LeeHM, LeeSH, SonJW, et al. (2010) Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signaling. Cell Microbiol 12 : 1648–1665.

6. PecoraND, GehringAJ, CanadayDH, BoomWH, HardingCV (2006) Mycobacterium tuberculosis LprA is a lipoprotein agonist of TLR2 that regulates innate immunity and APC function. J Immunol 177 : 422–429.

7. GehringAJ, DobosKM, BelisleJT, HardingCV, BoomWH (2004) Mycobacterium tuberculosis LprG (Rv1411c): A novel TLR-2 ligand that inhibits human macrophage class II MHC antigen processing. J Immunol 173 : 2660–2668.

8. PaiRK, ConveryM, HamiltonTA, BoomWH, HardingCV (2003) Inhibition of IFN-gamma-induced class II transactivator expression by a 19-kDa lipoprotein from Mycobacterium tuberculosis: a potential mechanism for immune evasion. J Immunol 171 : 175–184.

9. NossEH, PaiRK, SellatiTJ, RadolfJD, BelisleJ, et al. (2001) Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19 kD lipoprotein of Mycobacterium tuberculosis. J Immunol 167 : 910–918.

10. BrennanPJ (2003) Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 83 : 91–97.

11. BergS, KaurD, JacksonM, BrennanPJ (2007) The glycosyltransferases of Mycobacterium tuberculosis -⁠ roles in the synthesis of arabinogalactan, lipoarabinomannan, and other glycoconjugates. Glycobiology 17 : 35–56R.

12. MakarovV, ManinaG, MikusovaK, MollmannU, RyabovaO, et al. (2009) Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science 324 : 801–804.

13. KangPB, AzadAK, TorrellesJB, KaufmanTM, BeharkaA, et al. (2005) The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J Exp Med 202 : 987–999.

14. VergneI, ChuaJ, DereticV (2003) Tuberculosis toxin blocking phagosome maturation inhibits a novel Ca2+/calmodulin-PI3K hVPS34 cascade. J Exp Med 198 : 653–659.

15. FrattiRA, ChuaJ, VergneI, DereticV (2003) Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci USA 100 : 5437–5442.

16. ClemensDL, HorwitzMA (1995) Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med 181 : 257–270.

17. VergneI, ChuaJ, LeeHH, LucasM, BelisleJ, et al. (2005) Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 102 : 4033–4038.

18. ChuaJ, VergneI, MasterS, DereticV (2004) A tale of two lipids: Mycobacterium tuberculosis phagosome maturation arrest. Curr Opin Microbiol 7 : 71–77.

19. GuerinME, KordulakovaJ, AlzariPM, BrennanPJ, JacksonM (2010) Molecular basis of phosphatidyl-myo-inositol mannoside biosynthesis and regulation in mycobacteria. J Biol Chem 285 : 33577–33583.

20. ColeST, BroschR, ParkhillJ, GarnierT, ChurcherC, et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393 : 537–544.

21. SutcliffeIC, HarringtonDJ (2004) Lipoproteins of Mycobacterium tuberculosis: an abundant and functionally diverse class of cell envelope components. FEMS Microbiol Rev 28 : 645–659.

22. RezwanM, GrauT, TschumiA, SanderP (2007) Lipoprotein synthesis in mycobacteria. Microbiology 153 : 652–658.

23. SanderP, RezwanM, WalkerB, RampiniSK, KroppenstedtRM, et al. (2004) Lipoprotein processing is required for virulence of Mycobacterium tuberculosis. Mol Microbiol 52 : 1543–1552.

24. BanaeiN, KincaidEZ, LinSY, DesmondE, JacobsWRJr, et al. (2009) Lipoprotein processing is essential for resistance of Mycobacterium tuberculosis to malachite green. Antimicrob Agents Chemother 53 : 3799–3802.

25. MalenH, PathakS, SoftelandT, de SouzaGA, WikerHG (2010) Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv. BMC Microbiol 10 : 132.

26. BigiF, AlitoA, RomanoMI, ZumarragaM, CaimiK, et al. (2000) The gene encoding P27 lipoprotein and a putative antibiotic-resistance gene form an operon in Mycobacterium tuberculosis and Mycobacterium bovis. Microbiology 146 (Pt 4) 1011–1018.

27. BigiF, GioffreA, KleppL, de la Paz SantangeloM, AlitoA, et al. (2004) The knockout of the lprG-Rv1410 operon produces strong attenuation of Mycobacterium tuberculosis. Microbes Infect 6 : 182–187.

28. BiancoMV, BlancoFC, ImperialeB, ForrelladMA, RochaRV, et al. (2011) Role of P27–P55 operon from Mycobacterium tuberculosis in the resistance to toxic compounds. BMC Infect Dis 11 : 195.

29. BiancoMV, BlancoFC, ForrelladMA, AguilarD, CamposE, et al. (2011) Knockout mutation of p27–p55 operon severely reduces replication of Mycobacterium bovis in a macrophagic cell line and survival in a mouse model of infection. Virulence 2 : 233–237.

30. FarrowMF, RubinEJ (2008) Function of a mycobacterial major facilitator superfamily pump requires a membrane-associated lipoprotein. J Bacteriol 190 : 1783–1791.

31. DrageMG, TsaiHC, PecoraND, ChengTY, AridaAR, et al. (2010) Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2. Nature Struct Mol Biol 17 : 1088–1095.

32. BigiF, EspitiaC, AlitoA, ZumarragaM, RomanoMI, et al. (1997) A novel 27 kDa lipoprotein antigen from Mycobacterium bovis. Microbiology 143 (Pt 11) 3599–3605.

33. JohnssonB, LofasS, LindquistG (1991) Immobilization of proteins to a carboxymethyldextran-modified gold surface for biospecific interaction analysis in surface plasmon resonance sensors. Anal Biochem 198 : 268–277.

34. SidobreS, NigouJ, PuzoG, RiviereM (2000) Lipoglycans are putative ligands for the human pulmonary surfactant protein A attachment to mycobacteria. Critical role of the lipids for lectin-carbohydrate recognition. J Biol Chem 275 : 2415–2422.