High affinity nanobodies against the trypanosome brucei VSG are potent trypanolytic agents that block endocytosis

PLoS Pathogens

Volumn 7, Issue 6, 2011, Pages

  Stijlemans, Benoît ^a,b   Caljon, Guy ^a,b,c   Natesan, Senthil Kumar A ^d   Saerens, Dirk ^a,b   Conrath, Katja ^a,b   Pérez Morga, David ^e   Skepper, Jeremy N ^d   Nikolaou, Alexandros ^a   Brys, Lea ^a,b   Pays, Etienne ^e   Magez, Stefan ^a,b   Field, Mark C ^d   de Baetselier, Patrick ^a,b   Muyldermans, Serge ^a,b  

^a VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c INSTITUTE OF TROPICAL MEDICINE   (Belgium)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^e UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTIBODY; ANTIVARIANT SURFACE GLYCOPROTEIN NANOBODY; IMMUNOGLOBULIN; MONOVALENT CATION; NANOBODY; PAPAIN; PROTEIN ANTIBODY; UNCLASSIFIED DRUG; VARIANT SURFACE GLYCOPROTEIN; ANTITRYPANOSOMAL AGENT; NANOPARTICLE; PROTOZOON ANTIBODY;

ANIMAL EXPERIMENT; ANTIGEN BINDING; ARTICLE; CELL DEATH; CELL MOTILITY; CONTROLLED STUDY; ENDOCYTOSIS; ENZYME RECONSTITUTION; LYSIS; MITOCHONDRIAL MEMBRANE POTENTIAL; MOLECULAR WEIGHT; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PROTEIN DEGRADATION; PROTEIN MODIFICATION; SITE DIRECTED MUTAGENESIS; TRYPANOLYTIC ACTIVITY; TRYPANOSOMA BRUCEI; AFRICAN TRYPANOSOMIASIS; AMINO ACID SEQUENCE; ANIMAL; ANTIBODY AFFINITY; BIOLOGICAL MODEL; C57BL MOUSE; CELL CULTURE; CHEMICAL STRUCTURE; DOWN REGULATION; DRUG EFFECT; EVALUATION; HUMAN; IMMUNOLOGY; METABOLISM; MOLECULAR GENETICS; PHYSIOLOGY; ULTRASTRUCTURE;

CAMELIDAE; MAMMALIA; TRYPANOSOMA BRUCEI;

AMINO ACID SEQUENCE; ANIMALS; ANTIBODIES, PROTOZOAN; ANTIBODY AFFINITY; CELLS, CULTURED; DOWN-REGULATION; ENDOCYTOSIS; HUMANS; MICE; MICE, INBRED C57BL; MODELS, BIOLOGICAL; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NANOPARTICLES; TRYPANOCIDAL AGENTS; TRYPANOSOMA BRUCEI BRUCEI; TRYPANOSOMIASIS, AFRICAN; VARIANT SURFACE GLYCOPROTEINS, TRYPANOSOMA;

EID: 79959851947     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1002072     Document Type: Article

References (60)

1. Barrett MP, Burchmore RJ, Stich A, Lazzari JO, Frasch AC, et al. (2003) The trypanosomiases. Lancet 362: 1469-1480.
2. Sternberg JM, (2004) Human African trypanosomiasis: clinical presentation and immune response. Parasite Immunol 26: 469-476.
3. Donelson JE, Hill KL, El-Sayed NM, (1998) Multiple mechanisms of immune evasion by African trypanosomes. Mol Biochem Parasitol 91: 51-66.
4. Vanhamme L, Pays E, McCulloch R, Barry JD, (2001) An update on antigenic variation in African trypanosomes. Trends Parasitol 17: 338-343.
5. Jackson DG, Owen MJ, Voorheis HP, (1985) A new method for the rapid purification of both the membrane-bound and released forms of the variant surface glycoprotein from Trypanosoma brucei. Biochem J 230: 195-202.
6. Barry JD, McCulloch R, (2001) Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Adv Parasitol 49: 1-70.
7. Russo DC, Williams DJ, Grab DJ, (1994) Mechanisms for the elimination of potentially lytic complement-fixing variable surface glycoprotein antibody-complexes in Trypanosoma brucei. Parasitol Res 80: 487-492.
8. Pal A, Hall BS, Jeffries TR, Field MC, (2003) Rab5 and Rab11 mediate transferrin and anti-variant surface glycoprotein antibody recycling in Trypanosoma brucei. Biochem J 374: 443-451.
9. Webster P, Russo DC, Black SJ, (1990) The interaction of Trypanosoma brucei with antibodies to variant surface glycoproteins. J Cell Sci 96 (Pt 2): 249-255.
10. Balber AE, Bangs JD, Jones SM, Proia RL, (1979) Inactivation or elimination of potentially trypanolytic, complement-activating immune complexes by pathogenic trypanosomes. Infect Immun 24: 617-627.
11. O'Beirne C, Lowry CM, Voorheis HP, (1998) Both IgM and IgG anti-VSG antibodies initiate a cycle of aggregation-disaggregation of bloodstream forms of Trypanosoma brucei without damage to the parasite. Mol Biochem Parasitol 91: 165-193.
12. Engstler M, Pfohl T, Herminghaus S, Boshart M, Wiegertjes G, et al. (2007) Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 131: 505-515.
13. Field MC, Carrington M, (2009) The trypanosome flagellar pocket. Nat Rev Microbiol 7: 775-786.
14. Frevert U, Reinwald E, (1990) Trypanosoma congolense bloodstream forms evade complement lysis in vitro by shedding of immune complexes. Eur J Cell Biol 52: 264-269.
15. Takayanagi T, Kawaguchi H, Yabu Y, Itoh M, Yano K, (1991) Dissociation of IgG antibody-mediated clumps of Trypanosoma brucei gambiense by complement. Parasitol Res 77: 645-650.
16. Ralston KS, Kabututu ZP, Melehani JH, Oberholzer M, Hill KL, (2009) The Trypanosoma brucei flagellum: moving parasites in new directions. Annu Rev Microbiol 63: 335-362.
17. Grunfelder CG, Engstler M, Weise F, Schwarz H, Stierhof YD, et al. (2002) Accumulation of a GPI-anchored protein at the cell surface requires sorting at multiple intracellular levels. Traffic 3: 547-559.
18. Gull K, (2003) Host-parasite interactions and trypanosome morphogenesis: a flagellar pocketful of goodies. Curr Opin Microbiol 6: 365-370.
19. Thilo L, (1985) Quantification of endocytosis-derived membrane traffic. Biochim Biophys Acta 822: 243-266.
20. Engstler M, Thilo L, Weise F, Grunfelder CG, Schwarz H, et al. (2004) Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei. J Cell Sci 117: 1105-1115.
21. Kabiri M, Steverding D, (2000) Studies on the recycling of the transferrin receptor in Trypanosoma brucei using an inducible gene expression system. Eur J Biochem 267: 3309-3314.
22. Overath P, Engstler M, (2004) Endocytosis, membrane recycling and sorting of GPI-anchored proteins: Trypanosoma brucei as a model system. Mol Microbiol 53: 735-744.
23. Grunfelder CG, Engstler M, Weise F, Schwarz H, Stierhof YD, et al. (2003) Endocytosis of a glycosylphosphatidylinositol-anchored protein via clathrin-coated vesicles, sorting by default in endosomes, and exocytosis via RAB11-positive carriers. Mol Biol Cell 14: 2029-2040.
24. Jeffries TR, Morgan GW, Field MC, (2001) A developmentally regulated rab11 homologue in Trypanosoma brucei is involved in recycling processes. J Cell Sci 114: 2617-2626.
25. Brighouse A, Dacks JB, Field MC, (2010) Rab protein evolution and the history of the eukaryotic endomembrane system. Cell Mol Life Sci 67: 3449-3465.
26. Pal A, Hall BS, Nesbeth DN, Field HI, Field MC, (2002) Differential endocytic functions of Trypanosoma brucei Rab5 isoforms reveal a glycosylphosphatidylinositol-specific endosomal pathway. J Biol Chem 277: 9529-9539.
27. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, et al. (1993) Naturally occurring antibodies devoid of light chains. Nature 363: 446-448.
28. Muyldermans S, (2001) Single domain camel antibodies: current status. J Biotechnol 74: 277-302.
29. Saerens D, Ghassabeh GH, Muyldermans S, (2008) Single-domain antibodies as building blocks for novel therapeutics. Curr Opin Pharmacol 8: 600-608.
30. Stijlemans B, Conrath K, Cortez-Retamozo V, Van Xong H, Wyns L, et al. (2004) Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. African trypanosomes as paradigm. J Biol Chem 279: 1256-1261.
31. Baral TN, Magez S, Stijlemans B, Conrath K, Vanhollebeke B, et al. (2006) Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor. Nat Med 12: 580-584.
32. Allen CL, Goulding D, Field MC, (2003) Clathrin-mediated endocytosis is essential in Trypanosoma brucei. Embo J 22: 4991-5002.
33. Seyfang A, Mecke D, Duszenko M, (1990) Degradation, recycling, and shedding of Trypanosoma brucei variant surface glycoprotein. J Protozool 37: 546-552.
34. Ter Kuile BH, Wiemer EA, Michels PA, Opperdoes FR, (1992) The electrochemical proton gradient in the bloodstream form of Trypanosoma brucei is dependent on the temperature. Mol Biochem Parasitol 55: 21-27.
35. Barrett MP, Tetaud E, Seyfang A, Bringaud F, Baltz T, (1998) Trypanosome glucose transporters. Mol Biochem Parasitol 91: 195-205.
36. Miletti LC, Koerich LB, Pacheco LK, Steindel M, Stambuk BU, (2006) Characterization of D-glucose transport in Trypanosoma rangeli. Parasitology 133: 721-727.
37. Wilcke M, Johannes L, Galli T, Mayau V, Goud B, et al. (2000) Rab11 regulates the compartmentalization of early endosomes required for efficient transport from early endosomes to the trans-golgi network. J Cell Biol 151: 1207-1220.
38. Hall B, Allen CL, Goulding D, Field MC, (2004) Both of the Rab5 subfamily small GTPases of Trypanosoma brucei are essential and required for endocytosis. Mol Biochem Parasitol 138: 67-77.
39. Delafosse A, Doutoum AA, (2004) Prevalence of Trypanosoma evansi infection and associated risk factors in camels in eastern Chad. Vet Parasitol 119: 155-164.
40. Desmyter A, Spinelli S, Payan F, Lauwereys M, Wyns L, et al. (2002) Three camelid VHH domains in complex with porcine pancreatic alpha-amylase. Inhibition and versatility of binding topology. J Biol Chem 277: 23645-23650.
41. Transue TR, De Genst E, Ghahroudi MA, Wyns L, Muyldermans S, (1998) Camel single-domain antibody inhibits enzyme by mimicking carbohydrate substrate. Proteins 32: 515-522.
42. Stockwin LH, Holmes S, (2003) Antibodies as therapeutic agents: vive la renaissance! Expert Opin Biol Ther 3: 1133-1152.
43. Nevinsky GA, Buneva VN, (2003) Catalytic antibodies in healthy humans and patients with autoimmune and viral diseases. J Cell Mol Med 7: 265-276.
44. Wentworth P Jr, Jones LH, Wentworth AD, Zhu X, Larsen NA, et al. (2001) Antibody catalysis of the oxidation of water. Science 293: 1806-1811.
45. Datta D, Vaidehi N, Xu X, Goddard WA 3rd, (2002) Mechanism for antibody catalysis of the oxidation of water by singlet dioxygen. Proc Natl Acad Sci U S A 99: 2636-2641.
46. Wentworth AD, Jones LH, Wentworth P Jr, Janda KD, Lerner RA, (2000) Antibodies have the intrinsic capacity to destroy antigens. Proc Natl Acad Sci U S A 97: 10930-10935.
47. Hall BS, Smith E, Langer W, Jacobs LA, Goulding D, et al. (2005) Developmental variation in Rab11-dependent trafficking in Trypanosoma brucei. Eukaryot Cell 4: 971-980.
48. Lorger M, Engstler M, Homann M, Goringer HU, (2003) Targeting the variable surface of African trypanosomes with variant surface glycoprotein-specific, serum-stable RNA aptamers. Eukaryot Cell 2: 84-94.
49. McGwire BS, Olson CL, Tack BF, Engman DM, (2003) Killing of African trypanosomes by antimicrobial peptides. J Infect Dis 188: 146-152.
50. Delgado M, Anderson P, Garcia-Salcedo JA, Caro M, Gonzalez-Rey E, (2009) Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death. Cell Death Differ 16: 406-416.
51. Haines LR, Thomas JM, Jackson AM, Eyford BA, Razavi M, et al. (2009) Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18. PLoS Negl Trop Dis 3: e373.
52. Natesan SK, Peacock L, Leung KF, Gibson W, Field MC, (2010) Evidence that low endocytic activity is not directly responsible for human serum resistance in the insect form of African trypanosomes. BMC Res Notes 3: 63.
53. Broadhead R, Dawe HR, Farr H, Griffiths S, Hart SR, et al. (2006) Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 440: 224-227.
54. Conrath KE, Lauwereys M, Galleni M, Matagne A, Frere JM, et al. (2001) Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae. Antimicrob Agents Chemother 45: 2807-2812.
55. Hmila I, Abdallah RB, Saerens D, Benlasfar Z, Conrath K, et al. (2008) VHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI'. Mol Immunol 45: 3847-3856.
56. Natesan SK, Peacock L, Matthews K, Gibson W, Field MC, (2007) Activation of endocytosis as an adaptation to the mammalian host by trypanosomes. Eukaryot Cell 6: 2029-2037.
57. Saerens D, Frederix F, Reekmans G, Conrath K, Jans K, et al. (2005) Engineering camel single-domain antibodies and immobilization chemistry for human prostate-specific antigen sensing. Anal Chem 77: 7547-7555.
58. Field MC, Allen CL, Dhir V, Goulding D, Hall BS, et al. (2004) New approaches to the microscopic imaging of Trypanosoma brucei. Microsc Microanal 10: 621-636.
59. Bayele HK, (2001) Triazinyl derivatives that are potent inhibitors of glucose transport in Trypanosoma brucei. Parasitol Res 87: 911-914.
60. Bradford MM, (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254.