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Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System


Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis.


Vyšlo v časopise: Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System. PLoS Pathog 7(10): e32767. doi:10.1371/journal.ppat.1002340
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002340

Souhrn

Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis.


Zdroje

1. CokerRRushtonJMounier-JackSKarimuriboELutumbaP 2011 Towards a conceptual framework to support one-health research for policy on emerging zoonoses. Lancet Infect Dis 11 326 331

2. VanhammeLPaturiaux-HanocqFPoelvoordePNolanDPLinsL 2003 Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature 422 83 87

3. XongHVVanhammeLChamekhMChimfwembeCEVan Den AbbeeleJ 1998 A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 95 839 846

4. KieftRCapewellPTurnerCMVeitchNJMacLeodA 2010 Mechanism of Trypanosoma brucei gambiense (group 1) resistance to human trypanosome lytic factor. Proc Natl Acad Sci USA 107 16137 16141

5. KennedyMJ 1988 Alberta. Trypanosoma theileri in cattle of central Alberta. Can Vet J 29 937 938

6. MatthewsDMKingstonNMakiLNelmsG 1979 Trypanosoma theileri Laveran, 1902, in Wyoming cattle. Am J Vet Res 40 623 629

7. WooPSoltysMAGillickAC 1970 Trypanosomes in cattle in southern Ontario. Can J Comp Med 34 142 147

8. VillaAGutierrezCGraciaEMorenoBChaconG 2008 Presence of Trypanosoma theileri in Spanish Cattle. Ann N Y Acad Sci 1149 352 354

9. NiakA 1978 The incidence of Trypanosoma theileri among cattle in Iran. Trop Anim Health Prod 10 26 27

10. FarrarRGKleiTR 1990 Prevalence of Trypanosoma theileri in Louisiana cattle. J Parasitol 76 734 736

11. VerlooDBrandtJVan MeirvenneNBuscherP 2000 Comparative in vitro isolation of Trypanosoma theileri from cattle in Belgium. Vet Parasitol 89 129 132

12. RisticMTragerW 1958 Cultivation at 37°C of a Trypanosome (Trypanosoma theileri) from Cows with Depressed Milk Production. J Protozool 2 146 148

13. DohertyMLWindleHVoorheisHPLarkinHCaseyM 1993 Clinical disease associated with Trypanosoma theileri infection in a calf in Ireland. Vet Rec 132 653 656

14. Lanevschi-PietersmaAOgunremiODesrocherA 2004 Parasitemia in a neonatal bison calf. Vet Clin Pathol 33 173 176

15. SeifiHA 1995 Clinical trypanosomosis due to Trypanosoma theileri in a cow in Iran. Trop Anim Health Pro 27 93 94

16. BoseRFriedhoffKTOlbrichSBuscherGDomeyerI 1987 Transmission of Trypanosoma theileri to cattle by Tabanidae. Parasitol Res 73 421 424

17. RobertssonJALindbergAAHoisethSStockerBA 1983 Salmonella typhimurium infection in calves: protection and survival of virulent challenge bacteria after immunization with live or inactivated vaccines. Infect Immun 41 742 750

18. HoisethSKStockerBA 1981 Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature 291 238 239

19. BarlettaRGSnapperBCirilloJDConnellNDKimDD 1990 Recombinant BCG as a candidate oral vaccine vector. Res Microbiol 141 931 939

20. ChenTMMazaitisAJMaasWK 1985 Construction of a conjugative plasmid with potential use in vaccines against heat-labile enterotoxin. Infect Immun 47 5 10

21. RadfordKJJacksonAMWangJHVassauxGLemoineNR 2003 Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: presentation of MART1 to CD8+ T cells. Int J Cancer 105 811 819

22. SizemoreDRBranstromAASadoffJC 1995 Attenuated Shigella as a DNA delivery vehicle for DNA-mediated immunization. Science 270 299 302

23. GullK 1999 The cytoskeleton of trypanosomatid parasites. Annu Rev Microbiol 53 629 655

24. BorstP 1986 Discontinuous transcription and antigenic variation in trypanosomes. Annu Rev Biochem 55 701 732

25. TschudiCUlluE 1994 Trypanosomatid protozoa provide paradigms of eukaryotic biology. Infect Agents Dis 3 181 186

26. GibsonWBingleLBlendemanWBrownJWoodJ 2000 Structure and sequence variation of the trypanosome spliced leader transcript. Mol Biochem Parasitol 107 269 277

27. El-SayedNMMylerPJBlandinGBerrimanMCrabtreeJ 2005 Comparative genomics of trypanosomatid parasitic protozoa. Science 309 404 409

28. BangsJDBrouchEMRansomDMRoggyJL 1996 A soluble secretory reporter system in Trypanosoma brucei. Studies on endoplasmic reticulum targeting. J Biol Chem 271 18387 18393

29. DelbecqSPrecigoutEValletACarcyBSchettersTP 2002 Babesia divergens: cloning and biochemical characterization of Bd37. Parasitol 125 305 312

30. BrownWCNorimineJGoffWLSuarezCEMcElwainTF 2006 Prospects for recombinant vaccines against Babesia bovis and related parasites. Parasite Immunol 28 315 327

31. GoffWLWagnerGGCraigTM 1984 Increased activity of bovine ADCC effector cells during acute Babesia bovis infection. Vet Parasitol 16 5 15

32. GoffWLWagnerGGCraigTMLongRF 1984 The role of specific immunoglobulins in antibody-dependent cell-mediated cytotoxicity assays during Babesia bovis infection. Vet Parasitol 14 117 128

33. PrecigoutEDelbecqSValletACarcyBCamillieriS 2004 Association between sequence polymorphism in an epitope of Babesia divergens Bd37 exoantigen and protection induced by passive transfer. Int J Parasitol 34 585 593

34. Hadj-KaddourKCarcyBValletARandazzoSDelbecqS 2007 Recombinant protein Bd37 protected gerbils against heterologous challenges with isolates of Babesia divergens polymorphic for the bd37 gene. Parasitol 134 187 196

35. ClaytonCE 1999 Genetic manipulation of kinetoplastida. Parasitol Today 15 372 378

36. BiebingerSWirtzLELorenzPClaytonC 1997 Vectors for inducible expression of toxic gene products in bloodstream and procyclic Trypanosoma brucei. Mol Biochem Parasitol 85 99 112

37. KellyJMWardHMMilesMAKendallG 1992 A shuttle vector which facilitates the expression of transfected genes in Trypanosoma cruzi and Leishmania. Nucl Acids Res 20 3963 3969

38. TetaudELecuixISheldrakeTBaltzTFairlambAH 2002 A new expression vector for Crithidia fasciculata and Leishmania. Mol Biochem Parasitol 120 195 204

39. CoburnCMOttemanKMMcNeelyTTurcoSJBeverleySM 1991 Stable DNA transfection of a wide range of trypanosomatids. Mol Biochem Parasitol 46 169 179

40. FurgerAJungiTWSalomoneJYWeynantsVRoditiI 2001 Stable expression of biologically active recombinant bovine interleukin-4 in Trypanosoma brucei. FEBS letters 508 90 94

41. ClaytonCEHaSRuscheLHartmannCBeverleySM 2000 Tests of heterologous promoters and intergenic regions in Leishmania major. Mol Biochem Parasitol 105 163 167

42. BrueggemannABPaiRCrookDWBeallB 2007 Vaccine escape recombinants emerge after pneumococcal vaccination in the United States. PLoS Pathog 3 e168

43. SchlaferDH 1979 Trypanosoma theileri: a literature review and report of incidence in New York cattle. Cornell Vet 69 411 425

44. ThomsonRMolina-PortelaPMottHCarringtonMRaperJ 2009 Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both animal and human-infective African trypanosomes. Proc Natl Acad Sci U S A 106 19509 19514

45. LecordierLVanhollebekeBPoelvoordePTebabiPPaturiaux-HanocqF 2009 C-terminal mutants of apolipoprotein L-I efficiently kill both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense. PLoS Pathog 5 e1000685

46. HirumiHHirumiK 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

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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