A Tick Gut Protein with Fibronectin III Domains Aids Congregation to the Gut during Transmission

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Lyme borreliosis, the most common vector-borne illness in Northeastern parts of USA, is caused by Borrelia burgdorferi sensu lato spirochetes, and transmitted by the Ixodes scapularis ticks. Currently there is no vaccine available to prevent Lyme borreliosis. A better understanding of tick proteins that interact with Borrelia to facilitate spirochete transmission could identify new targets for the development of a tick-based vaccine to prevent Lyme borreliosis. Spirochete growth and exit from the gut is central to transmission, and might involve intimate interactions between the spirochete and the tick gut. We therefore performed a global screen to identify Borrelia-interacting tick gut proteins. One of the four Borrelia-interacting tick proteins, referred to as Ixofin3D, was further characterized. RNA-interference-mediated down-regulation of Ixofin3D resulted in decreased spirochete numbers in the salivary glands and consequently decreased transmission to the host during tick feeding. We demonstrate that Ixofin3D aids spirochete congregation to the gut epithelium, a critical first step that might direct spirochete exit from the gut.

Vyšlo v časopise: A Tick Gut Protein with Fibronectin III Domains Aids Congregation to the Gut during Transmission. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004278
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004278

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Zdroje

1. Estrada-PenaA, JongejanF (1999) Ticks feeding on humans: a review of records on human-biting Ixodoidea with special reference to pathogen transmission. Exp Appl Acarol 23 : 685–715.

2. de la FuenteJ, Estrada-PenaA, VenzalJM, KocanKM, SonenshineDE (2008) Overview: Ticks as vectors of pathogens that cause disease in humans and animals. Front Biosci 13 : 6938–6946.

3. PlotkinSA (2011) Correcting a public health fiasco: The need for a new vaccine against Lyme disease. Clin Infect Dis 52 Suppl 3: s271–275.

4. WressniggN, PollabauerEM, AichingerG, PortsmouthD, Low-BaselliA, et al. (2013) Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial. Lancet Infect Dis 13 : 680–689.

5. HoviusJW, van DamAP, FikrigE (2007) Tick-host-pathogen interactions in Lyme borreliosis. Trends Parasitol 23 : 434–438.

6. SchuijtTJ, HoviusJW, van der PollT, van DamAP, FikrigE (2011) Lyme borreliosis vaccination: the facts, the challenge, the future. Trends Parasitol 27 : 40–47.

7. de la FuenteJ, KocanKM, AlmazanC, BlouinEF (2008) Targeting the tick-pathogen interface for novel control strategies. Front Biosci 13 : 6947–6956.

8. PalU, LiX, WangT, MontgomeryRR, RamamoorthiN, et al. (2004) TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi. Cell 119 : 457–468.

9. PiesmanJ, MatherTN, SinskyRJ, SpielmanA (1987) Duration of tick attachment and Borrelia burgdorferi transmission. J Clin Microbiol 25 : 557–558.

10. RosaPA, TillyK, StewartPE (2005) The burgeoning molecular genetics of the Lyme disease spirochaete. Nat Rev Microbiol 3 : 129–143.

11. RadolfJD, CaimanoMJ, StevensonB, HuLT (2012) Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nat Rev Microbiol 10 : 87–99.

12. RudenkoN, GolovchenkoM, EdwardsMJ, GrubhofferL (2005) Differential expression of Ixodes ricinus tick genes induced by blood feeding or Borrelia burgdorferi infection. J Med Entomol 42 : 36–41.

13. Dunham-EmsSM, CaimanoMJ, PalU, WolgemuthCW, EggersCH, et al. (2009) Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. J Clin Invest 119 : 3652–3665.

14. ZhangL, ZhangY, AdusumilliS, LiuL, NarasimhanS, et al. (2011) Molecular interactions that enable movement of the Lyme disease agent from the tick gut into the hemolymph. PLoS Pathog 7: e1002079.

15. PepperLR, ChoYK, BoderET, ShustaEV (2008) A decade of yeast surface display technology: where are we now? Comb Chem High Throughput Screen 11 : 127–134.

16. ChoYK, ShustaEV (2010) Antibody library screens using detergent-solubilized mammalian cell lysates as antigen sources. Protein Eng Des Sel 23 : 567–577.

17. TillotsonBJ, ChoYK, ShustaEV (2013) Cells and cell lysates: a direct approach for engineering antibodies against membrane proteins using yeast surface display. Methods 60 : 27–37.

18. NowalkAJ, NolderC, CliftonDR, CarrollJA (2006) Comparative proteome analysis of subcellular fractions from Borrelia burgdorferi by NEPHGE and IPG. Proteomics 6 : 2121–2134.

19. CoburnJ, LeongJ, ChaconasG (2013) Illuminating the roles of the Borrelia burgdorferi adhesins. Trends Microbiol 21 : 372–379.

20. PankovR, YamadaKM (2002) Fibronectin at a glance. J Cell Sci 115 : 3861–3863.

21. HendersonB, NairS, PallasJ, WilliamsMA (2011) Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding proteins. FEMS Microbiol Rev 35 : 147–200.

22. NarasimhanS, PerezO, MootienS, DeponteK, KoskiRA, et al. (2013) Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis. PLoS One 8: e68012.

23. NarasimhanS, SukumaranB, BozdoganU, ThomasV, LiangX, et al. (2007) A tick antioxidant facilitates the Lyme disease agent's successful migration from the mammalian host to the arthropod vector. Cell Host Microbe 2 : 7–18.

24. SchmitVL, PattonTG, GilmoreRDJr (2011) Analysis of Borrelia burgdorferi Surface Proteins as Determinants in Establishing Host Cell Interactions. Front Microbiol 2 : 141.

25. SchwanTG, PiesmanJ (2002) Vector interactions and molecular adaptations of lyme disease and relapsing fever spirochetes associated with transmission by ticks. Emerg Infect Dis 8 : 115–121.

26. De SilvaAM, FikrigE (1995) Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding. Am J Trop Med Hyg 53 : 397–404.

27. SkorstengaardK, JensenMS, SahlP, PetersenTE, MagnussonS (1986) Complete primary structure of bovine plasma fibronectin. Eur J Biochem 161 : 441–453.

28. BrissetteCA, BykowskiT, CooleyAE, BowmanA, StevensonB (2009) Borrelia burgdorferi RevA antigen binds host fibronectin. Infect Immun 77 : 2802–2812.

29. LiX, LiuX, BeckDS, KantorFS, FikrigE (2006) Borrelia burgdorferi lacking BBK32, a fibronectin-binding protein, retains full pathogenicity. Infect Immun 74 : 3305–3313.

30. SeshuJ, Esteve-GassentMD, Labandeira-ReyM, KimJH, TrzeciakowskiJP, et al. (2006) Inactivation of the fibronectin-binding adhesin gene bbk32 significantly attenuates the infectivity potential of Borrelia burgdorferi. Mol Microbiol 59 : 1591–1601.

31. ChaoG, LauWL, HackelBJ, SazinskySL, LippowSM, et al. (2006) Isolating and engineering human antibodies using yeast surface display. Nat Protoc 1 : 755–768.

32. SchuijtTJ, NarasimhanS, DaffreS, DePonteK, HoviusJW, et al. (2011) Identification and characterization of Ixodes scapularis antigens that elicit tick immunity using yeast surface display. PLoS One 6: e15926.

33. HoviusJW, RamamoorthiN, Van't VeerC, de GrootKA, NijhofAM, et al. (2007) Identification of Salp15 homologues in Ixodes ricinus ticks. Vector Borne Zoonotic Dis 7 : 296–303.

34. SchultzJ, MilpetzF, BorkP, PontingCP (1998) SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci U S A 95 : 5857–5864.

35. SchuijtTJ, CoumouJ, NarasimhanS, DaiJ, DeponteK, et al. (2011) A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent. Cell Host Microbe 10 : 136–146.

36. AltschulSF, MaddenTL, SchafferAA, ZhangJ, ZhangZ, et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25 : 3389–3402.