Regulated expression of the Leishmania major surface virulence factor lipophosphoglycan using conditionally destabilized fusion proteins

Proceedings of the National Academy of Sciences of the United States of America

Volumn 106, Issue 18, 2009, Pages 7583-7588

  Silva, Luciana Madeira Da ^a   Owens, Katherine L ^a   Murta, Silvane M F ^a,b   Beverley, Stephen M ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b INSTITUTO OSWALDO CRUZ   (Brazil)

Author keywords

FK506; Glycoconjugates; Inducible expression; Pathogen trypanosomatid protozoa

Indexed keywords

CELL PROTEIN; FK 506 BINDING PROTEIN; HYBRID PROTEIN; LIPOPHOSPHOGLYCAN; MUTASE; RAPAMYCIN; TACROLIMUS; URIDINE DIPHOSPHATE GALACTOSE; GLYCOSPHINGOLIPID; UDP GALACTOPYRANOSE MUTASE; UDP-GALACTOPYRANOSE MUTASE; VIRULENCE FACTOR;

ARTICLE; CHROMOSOME; CONTROLLED STUDY; ENZYME DEGRADATION; EPISOME; GENE DELETION; KINETICS; LEISHMANIA MAJOR; MICROBIAL GROWTH; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN STABILITY; REGULATORY MECHANISM; SUBSTITUTION REACTION; ANIMAL; BIOSYNTHESIS; DOWN REGULATION; DRUG EFFECT; GENETICS; METABOLISM; PROTEIN TERTIARY STRUCTURE;

LEISHMANIA MAJOR; MAMMALIA; PHLEBOTOMINAE; PROTOZOA; TRYPANOSOMATIDAE;

ANIMALS; DOWN-REGULATION; GLYCOSPHINGOLIPIDS; INTRAMOLECULAR TRANSFERASES; LEISHMANIA MAJOR; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT FUSION PROTEINS; SIROLIMUS; TACROLIMUS BINDING PROTEINS; VIRULENCE FACTORS;

EID: 66149125717     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0901698106     Document Type: Article

References (46)

1. World Health Organization (2002) Urbanization: An increasing risk factor for leishmaniasis. Wkly Epidemiol Rec 77:365-370.
2. Beattie L, Evans KJ, Kaye PM, Smith DF (2008) Transgenic Leishmania and the immune response to infection. Parasite Immunol 30:255-266.
3. Beverley SM (2003) Protozomics: Trypanosomatid parasite genetics comes of age. Nat Rev Genet 4:11-19.
4. Yan S, Myler PJ, Stuart K (2001) Tetracycline regulated gene expression in Leishmania donovani. Mol Biochem Parasitol 112:61-69.
5. Campbell DA, Thomas S, Sturm NR (2003) Transcription in kinetoplastid protozoa: Why be normal? Microbes Infect 5:1231-1240.
6. Clayton CE (2002) Life without transcriptional control? From fly to man and back again. EMBOJ 21:1881-1888.
7. Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ (2006) A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell 126:995-1004.
8. Armstrong CM, Goldberg DE (2007) An FKBP destabilization domain modulates protein levels in Plasmodium falciparum. Nat Methods 4:1007-1009.
9. Herm-Gotz A, etal. (2007) Rapid control ofprotein level in the apicomplexan Toxoplasma gondii. Nat Methods 4:1003-1005.
10. Naderer T, Vince JE, McConville MJ (2004) Surface determinants of Leishmania parasites and their role in infectivity in the mammalian host. CurrMol Med 4:649-665.
11. Beverley SM, Turco SJ (1998) Lipophosphoglycan (LPG) and the identification of virulence genes in the protozoan parasite Leishmania.Trends Microbiol 6:35-40.
12. Kamhawi S, et al. (2004) A role for insect galectins in parasite survival. Cell 119:329-341.
13. Spath GF, et al. (2003) Persistence without pathology in phosphoglycan-deficient Leish- mania major. Science 301:1241-1243.
14. Lodge R, Diallo TO, DescoteauxA(2006) Leishmania donovani lipophosphoglycan blocks NADPH oxidase assembly at the phagosome membrane. Cell Microbiol 8:1922-1931.
15. Lodge R, DescoteauxA(2005) Modulation of phagolysosome biogenesisbythe lipophos- phoglycan of Leishmania. Clin Immunol 114:256-265.
16. BeverleySM, etal. (2005)EukaryoticUDP-galactopyranose mutase (GLFgene)in microbial and metazoal pathogens. Eukaryot Cell 4:1147-1154.
17. Capul AA, Barron T, Dobson DE, Turco SJ, BeverleySM (2007) Two functionallydivergent UDP-Gal nucleotide sugar transporters participate in phosphoglycan synthesis in Leish- mania major. JBiol Chem 282:14006-14017.
18. Kleczka B,etal. (2007)Targeted gene deletion ofLeishmania majorUDP-galactopyranose mutase leads to attenuated virulence. JBiol Chem 282:10498-10505.
19. Spath GF, Garraway LA, Turco SJ, Beverley SM (2003) The role(s) of lipophosphoglycan (LPG) in the establishmentof Leishmania majorinfections in mammalian hosts. ProcNatl Acad Sci USA 100:9536-9541.
20. IlgoutzSC, McConvilleMJ (2001)Function and assemblyoftheLeishmaniasurface coat. Int JParasitol 31:899-908.
21. Turco SJ, etal. (1989) Structure of the phosphosaccharide-inositol core of the Leishmania donovani lipophosphoglycan. JBiol Chem 264:6711-6715.
22. Pedersen LL, Turco SJ (2003) Galactofuranose metabolism: Apotential targetfor antimicrobial chemotherapy. Cell Mol Life Sci 60:259-266.
23. Bakker H, Kleczka B, Gerardy-Schahn R, Routier FH (2005) Identification and partial characterization of two eukaryotic UDP-galactopyranose mutases. Biol Chem 386:657-661.
24. Zufferey R, et al. (2003) Ether phospholipids and glycosylinositolphospholipids are not required for amastigote virulence or for inhibition ofmacrophage activation byLeishma- nia major. JBiol Chem 278:44708-44718.
25. Spath GF, et al. (2000) Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major. Proc Natl Acad Sci USA 97:9258-9263.
26. Cardenas ME, et al. (1999) Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to studydrug action. Clin Microbiol Rev 12:583-611.
27. Cruz MC, etal. (1999) Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans. Mol Cell Biol 19:4101-4112.
28. Dumont FJ, Su Q (1996) Mechanism of action of the immunosuppressant rapamycin. Life Sci 58:373-395.
29. Meissner U, Juttner S, Rollinghoff M, Gessner A (2003) Cyclosporin A-mediated killing of Leishmania majorbymacrophages is independent of reactive nitrogen and endogenous TNF-alpha and is not inhibited byIL-10 and 13. Parasitol Res 89:221-227.
30. Cruz A, Coburn CM, BeverleySM (1991) Double targeted gene replacement for creating null mutants. Proc Natl Acad Sci USA 88:7170-7174.
31. Kapler GM, Coburn CM, Beverley SM (1990) Stable transfection of the human parasite Leishmania major delineates a 30-kilobase region sufficient for extrachromosomal replication and expression. Mol Cell Biol 10:1084-1094.
32. Misslitz A, Mottram JC, Overath P, Aebischer T (2000) Targeted integration into a rRNA locusresultsin uniform and high level expression oftransgenesin Leishmaniaamastigotes. Mol Biochem Parasitol 107:251-261.
33. Proudfoot L, Schneider P, Ferguson MA, McConville MJ (1995) Biosynthesis of the glyco- lipid anchor oflipophosphoglycan and the structurallyrelated glycoinositolphospholipids from Leishmania major. Biochem J308:45-55.
34. King DL, Chang YD, Turco SJ (1987) Cell surface lipophosphoglycan of Leishmania dono- vani. Mol Biochem Parasitol 24:47-53.
35. McKean PG, Denny PW, Knuepfer E, Keen JK, Smith DF (2001) Phenotypic changes associated with deletion and overexpression of a stage-regulated gene family in Leish- mania. Cell Microbiol 3:511-523.
36. Lincoln LM, Ozaki M, Donelson JE, Beetham JK (2004) Genetic complementation of Leishmania deficient in PSA (GP46) restores their resistance to lysis by complement. Mol Biochem Parasitol 137:185-189.
37. Joshi PB, Kelly BL, Kamhawi S, Sacks DL, McMaster WR (2002) Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. Mol Biochem Parasitol 120:33-40.
38. Liu J, et al. (1991) Calcineurin is a common targetof cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66:807-815.
39. Heitman J, Movva NR, Hall MN (1991) Targets for cell cycle arrestbythe immunosuppres- sant rapamycin in yeast. Science 253:905-909.
40. Sabers CJ, etal. (1995) Isolation of a protein target of the FKBP12-rapamycin complexin mammalian cells. JBiol Chem 270:815-822.
41. Luker KE, et al. (2004) Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. Proc Natl Acad Sci USA101:12288-12293.
42. Sacks D, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania majorin mice. Nat Rev Immunol 2:845-858.
43. Sacks DL, etal. (2000) The role of phosphoglycansin Leishmania-sand fly interactions. Proc Natl Acad Sci USA 97:406-411.
44. Sacks DL, Perkins PV (1984) Identification of an infective stage of Leishmania promastig-otes. Science 223:1417-1419.
45. Waller RF, McConville MJ (2002) Developmental changes in lysosome morphology and function in Leishmania. Int JParasitol 32:1435-1445.
46. Robinson KA, Beverley SM (2003) Improvements in transfection efficiency and tests of RNA interference (RNAi) approaches in the protozoan parasite Leishmania. Mol Biochem Parasitol 128:217-228.