The Gene Is Essential for Resistance to Human Serum in
Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense.
Vyšlo v časopise:
The Gene Is Essential for Resistance to Human Serum in. PLoS Pathog 9(10): e32767. doi:10.1371/journal.ppat.1003686
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1003686
Souhrn
Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense.
Zdroje
1. BarrettMP, BurchmoreRJS, StichA, LazzariJO, FraschAC, et al. (2003) The trypanosomiases. Lancet 362: 1469–1480 doi:10.1016/S0140-6736(03)14694-6
2. VincendeauP, BouteilleB (2006) Immunology and immunopathology of African trypanosomiasis. An Acad Bras Cienc 78: 645–665.
3. PaysE, VanhollebekeB (2009) Human innate immunity against African trypanosomes. Current Opinion in Immunology 21: 493–498.
4. PoelvoordeP, VanhammeL, AbbeeleJVD, SwitzerWM, PaysE (2004) Distribution of apolipoprotein L-I and trypanosome lytic activity among primate sera. Mol Biochem Parasitol 134: 155–157 doi:10.1016/j.molbiopara.2003.11.006
5. VanhammeL, Paturiaux-HanocqF, PoelvoordeP, NolanDP, LinsL, et al. (2003) Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature 422: 83–87 doi:10.1038/nature01461
6. RaperJ, PortelaMPM, LugliE, FrevertU, TomlinsonS (2001) Trypanosome lytic factors: novel mediators of human innate immunity. Current Opinion in Microbiology 4: 402–408.
7. VanhollebekeB, De MuylderG, NielsenMJ, PaysA, TebabiP, et al. (2008) A Haptoglobin-Hemoglobin Receptor Conveys Innate Immunity to Trypanosoma brucei in Humans. Science 320: 677–681 doi:10.1126/science.1156296
8. ShiflettAM, BishopJR, PahwaA, HajdukSL (2005) Human high density lipoproteins are platforms for the assembly of multi-component innate immune complexes. J Biol Chem 280: 32578–32585.
9. ShiflettA, FaulknerSD, CotlinLF, WidenerJ, StephensN, et al. (2007) African trypanosomes: intracellular trafficking of host defense molecules. J Eukaryot Microbiol 54: 18–21 doi:10.1111/j.1550-7408.2006.00228.x
10. CampilloN, CarringtonM (2003) The origin of the serum resistance associated (SRA) gene and a model of the structure of the SRA polypeptide from Trypanosoma brucei rhodesiense. Mol Biochem Parasitol 127: 79–84 doi:10.1016/S0166-6851(02)00306-7
11. BullardW, KieftR, CapewellP, VeitchNJ, MacleodA, et al. (2012) Haptoglobin-hemoglobin receptor independent killing of African trypanosomes by human serum. Virulence 3: 72–76.
12. SimarroPP, DiarraA, PostigoJAR, FrancoJR, JanninJG (2011) The Human African Trypanosomiasis Control and Surveillance Programme of the World Health Organization 2000–2009: The Way Forward. PLoS Neglected Tropical Diseases 5: e1007 doi:10.1371/journal.pntd.0001007
13. De GreefC, HamersR (1994) The serum resistance-associated (SRA) gene of Trypanosoma brucei rhodesiense encodes a variant surface glycoprotein-like protein. Mol Biochem Parasitol 68: 277–284.
14. XongHV, VanhammeL, ChamekhM, ChimfwembeCE, Van Den AbbeeleJ, et al. (1998) A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 95: 839–846.
15. De GreefC, ImberechtsH, MatthyssensG, Van MeirvenneN, HamersR (1989) A gene expressed only in serum-resistant variants of Trypanosoma brucei rhodesiense. Mol Biochem Parasitol 36: 169–176 doi:10.1016/0166-6851(89)90189-8
16. GibsonW (1986) Will the real Trypanosoma b. gambiense please stand up. Parasitol Today 2: 255–257.
17. KieftR, CapewellP, TurnerCMR, VeitchNJ, MacleodA, et al. (2010) Mechanism of Trypanosoma brucei gambiense (group 1) resistance to human trypanosome lytic factor. Proceedings of the National Academy of Sciences 107: 16137–16141.
18. DeJesusE, KieftR, AlbrightB, StephensNA, HajdukSL (2013) A Single Amino Acid Substitution in the Trypanosoma brucei gambiense Haptoglobin-Hemoglobin Receptor Abolishes TLF-1 Binding. PLoS Pathogens e1003317 doi:10.1371/journal.ppat.1003317
19. HigginsMK, TkachenkoO, BrownA (2013) Structure of the trypanosome haptoglobin–hemoglobin receptor and implications for nutrient uptake and innate immunity. Proceedings of the National Academy of Sciences 110 (5) 1905–10 doi:10.1073/pnas.1214943110/-/DCSupplemental
20. BerberofM, Pérez-MorgaD, PaysE (2001) A receptor-like flagellar pocket glycoprotein specific to Trypanosoma brucei gambiense. Mol Biochem Parasitol 113: 127–138.
21. GibsonW, NemetschkeL, Ndung'uJ (2010) Conserved sequence of the TgsGP gene in Group 1 Trypanosoma brucei gambiense. Infection, Genetics and Evolution 10: 453–458.
22. RadwanskaM, ClaesF, MagezS, MagnusE, Pérez-MorgaD, et al. (2002) Novel primer sequences for polymerase chain reaction-based detection of Trypanosoma brucei gambiense. Am J Trop Med Hyg 67: 289–295.
23. CapewellP, CooperA, DuffyCW, TaitA, TurnerCM, et al. (2013) Human and animal trypanosomes in Côte d'Ivoire form a single breeding population. PLoS ONE doi:10.1371/journal.pone.0067852
24. SymulaRE, BeadellJS, SistromM (2012) Trypanosoma brucei gambiense Group 1 Is Distinguished by a Unique Amino Acid Substitution in the HpHb Receptor Implicated in Human Serum Resistance. PLoS Neglected Tropical Diseases 6: e1728.
25. EisenhaberB, BorkP, EisenhaberF (1999) Prediction of Potential GPI-modification Sites in Proprotein Sequences. Journal of Molecular Biology 292: 741–758 doi:10.1006/jmbi.1999.3069
26. BöhmeU, CrossGAM (2002) Mutational analysis of the variant surface glycoprotein GPI-anchor signal sequence in Trypanosoma brucei. Journal of Cell Science 805–816.
27. BalberAE, FrommelTO (1988) Trypanosoma brucei gambiense and T. b. rhodesiense: Concanavalin A Binding to the Membrane and Flagellar Pocket of Bloodstream and Procyclic Forms. J Eukaryot Microbiol 35: 214–219 doi:10.1111/j.1550-7408.1988.tb04326.x
28. LecordierL, VanhollebekeB, PoelvoordeP, TebabiP, Paturiaux-HanocqF, et al. (2009) C-Terminal Mutants of Apolipoprotein L-I Efficiently Kill Both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense. PLoS Pathogens 5: e1000685 doi:10.1371/journal.ppat.1000685
29. GenoveseG, FriedmanDJ, RossMD, LecordierL, UzureauP, et al. (2010) Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans. Science 329: 841–845 doi:10.1126/science.1193032
30. Frezil JL (1983) Human trypanosomiasis in the Congo. Paris: ORSTOM.
31. JamonneauV, IlboudoH, KaboréJ, KabaD, KoffiM, et al. (2012) Untreated Human Infections by Trypanosoma brucei gambiense Are Not 100% Fatal. PLoS Neglected Tropical Diseases 6: e1691 doi:10.1371/journal.pntd.0001691
32. HirumiH, HirumiK (1989) Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers. J Parasitol 75: 985–989.
33. GiroudC, OttonesF, CoustouV, DacheuxD, BiteauN, et al. (2009) Murine Models for Trypanosoma brucei gambiense Disease Progression—From Silent to Chronic Infections and Early Brain Tropism. PLoS Neglected Tropical Diseases 3: e509 doi:10.1371/journal.pntd.0000509.t003
34. LigtenbergMJ, BitterW, KieftR, SteverdingD, JanssensH, et al. (1994) Reconstitution of a surface transferrin binding complex in insect form Trypanosoma brucei. The EMBO Journal 13: 2565.
35. BastinP, BagherzadehZ, MatthewsKR, GullK (1996) A novel epitope tag system to study protein targeting and organelle biogenesis in Trypanosoma brucei. Mol Biochem Parasitol 77: 235–239.
36. CapewellP, VeitchNJ, TurnerCMR, RaperJ, BerrimanM, et al. (2011) Differences between Trypanosoma brucei gambiense groups 1 and 2 in their resistance to killing by trypanolytic factor 1. PLoS Neglected Tropical Diseases 5: e1287.
37. AbràmoffMD, MagalhãesPJ, RamSJ (2004) Image processing with ImageJ. Biophotonics international 11: 36–42.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
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