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Applied Microbiology and Biotechnology

, Volume 102, Issue 8, pp 3663–3673 | Cite as

Nematode-specific cadherin CDH-8 acts as a receptor for Cry5B toxin in Caenorhabditis elegans

  • Donghai Peng
  • Danfeng Wan
  • Chunsheng Cheng
  • Xiaobo Ye
  • Ming Sun
Biotechnologically relevant enzymes and proteins

Abstract

Parasitic nematodes of animals and plants cause worldwide devastating impacts on people’s lives and agricultural crops. The crystal protein Cry5B produced by Bacillus thuringiensis has efficient and specific activity against a wide range of nematodes. However, the action mode of this toxin has not yet been thoroughly determined. Here, a nematode-specific cadherin CDH-8 was demonstrated to be a receptor for Cry5B toxin by using Caenorhabditis elegans as a model, providing evidence that the cadherin mutant worm cdh-8(RB815) possesses significant resistance to Cry5B, and the CDH-8 fragments bind specifically to Cry5B. Furthermore, CDH-8 was identified to be required for the oligomerization of Cry5B toxin in vivo and contribute to the internalization and pore formation of Cry5B in nematode cells. This study will facilitate a better understanding of the action mode of nematicidal Cry toxins and help the design of Cry toxin-based products for the control of plant or animal parasitic nematodes.

Keywords

Nematicidal crystal protein Caenorhabditis elegans Receptor Cadherin 

Notes

Acknowledgements

We thank Professor Hanchang Zhu (College of Foreign Language, Huazhong Agricultural University, Wuhan, China) for carefully proofreading this manuscript. This study was supported by the National Key R&D Program of China (2017YFD0200400 and 2017YFD0201201), the National Natural Science Foundation of China (31770116 and 31670085), and the Fundamental Research Funds for the Central Universities (2662016PY067).

Author contributions

DHP and MS designed the study and wrote the manuscript. DFW, CSC, XBY, and DHP participated in the experiments. DHP and DFW analyzed the data and contributed to the figures and tables. DFW performed the bioinformatic analysis. All authors have read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This research does not contain any studies with human participants or animals.

Supplementary material

253_2018_8868_MOESM1_ESM.pdf (490 kb)
ESM 1 (PDF 490 kb)

References

  1. Arenas I, Bravo A, Soberon M, Gomez I (2010) Role of alkaline phosphatase from Manduca sexta in the mechanism of action of Bacillus thuringiensis Cry1Ab toxin. J Biol Chem 285:12497–12503CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ (2006) Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 367:1521–1532CrossRefPubMedGoogle Scholar
  3. Bischof LJ, Huffman DL, Aroian RV (2006) Assays for toxicity studies in C. elegans with Bt crystal proteins. Methods Mol Biol 351:139–154PubMedGoogle Scholar
  4. Bravo A, Gomez I, Conde J, Munoz-Garay C, Sanchez J, Miranda R, Zhuang M, Gill SS, Soberon M (2004) Oligomerization triggers binding of a Bacillus thuringiensis Cry1Ab pore-forming toxin to aminopeptidase N receptor leading to insertion into membrane microdomains. Biochim Biophys Acta 1667:38–46CrossRefPubMedGoogle Scholar
  5. Bravo A, Gill SS, Soberon M (2007) Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control. Toxicon 49:423–435CrossRefPubMedGoogle Scholar
  6. Bravo A, Likitvivatanavong S, Gill SS, Soberon M (2011) Bacillus thuringiensis: a story of a successful bioinsecticide. Insect Biochem Mol Biol 41:423–431CrossRefPubMedPubMedCentralGoogle Scholar
  7. Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77:71–94PubMedPubMedCentralGoogle Scholar
  8. Chen J, Aimanova KG, Fernandez LE, Bravo A, Soberon M, Gill SS (2009) Aedes aegypti cadherin serves as a putative receptor of the Cry11Aa toxin from Bacillus thuringiensis subsp. israelensis. Biochem J 424:191–200CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dementiev A, Board J, Sitaram A, Hey T, Kelker MS, Xu XP, Hu Y, Vidal-Quist C, Chikwana V, Griffin S, McCaskill D, Wang NX, Hung SC, Chan MK, Lee MM, Hughes J, Wegener A, Aroian RV, Narva KE, Berry C (2016) The pesticidal Cry6Aa toxin from Bacillus thuringiensis is structurally similar to HlyE-family ɑ pore-forming toxins. BMC Biol 14:71CrossRefPubMedPubMedCentralGoogle Scholar
  10. Fabrick J, Oppert C, Lorenzen MD, Morris K, Oppert B, Jurat-Fuentes JL (2009) A novel Tenebrio molitor cadherin is a functional receptor for Bacillus thuringiensis Cry3Aa toxin. J Biol Chem 284:18401–18410CrossRefPubMedPubMedCentralGoogle Scholar
  11. Fire A, Xu S, Montgomery M, Kostas S, Driver S, Mello C (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811CrossRefPubMedGoogle Scholar
  12. Gomez I, Sanchez J, Miranda R, Bravo A, Soberon M (2002) Cadherin-like receptor binding facilitates proteolytic cleavage of helix K-1 in domain I and oligomer pre-pore formation of Bacillus thuringiensis Cry1Ab toxin. FEBS Lett 513:242–246CrossRefPubMedGoogle Scholar
  13. Griffitts JS, Whitacre JL, Stevens DE, Aroian RV (2001) Bt toxin resistance from loss of a putative carbohydrate-modifying enzyme. Science 293:860–864CrossRefPubMedGoogle Scholar
  14. Griffitts JS, Haslam SM, Yang T, Garczynski SF, Mulloy H, Morris H, Cremer PS, Dell A, Adang MJ, Aroian RV (2005) Glycolipids as receptors for Bacillus thuringiensis crystal toxin. Science 307:922–925CrossRefPubMedGoogle Scholar
  15. Guo S, Ye S, Liu Y, Wei L, Xue J, Wu H, Song F, Zhang J, Wu X, Huang D, Rao Z (2009) Crystal structure of Bacillus thuringiensis Cry8Ea1: an insecticidal toxin toxic to underground pests, the larvae of Holotrichia parallela. J Struct Biol 168:259–266CrossRefPubMedGoogle Scholar
  16. Hill E, Broadbent ID, Chothia C, Pettitt J (2001) Cadherin superfamily proteins in Caenorhabditis elegans and Drosophila melanogaster. J Mol Biol 305:1011–1024CrossRefPubMedGoogle Scholar
  17. Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118:1311–1321CrossRefPubMedPubMedCentralGoogle Scholar
  18. Hu Y, Georghiou SB, Kelleher AJ, Aroian RV (2010) Bacillus thuringiensis Cry5B protein is highly efficacious as a single-dose therapy against an intestinal roundworm infection in mice. PLoS Negl Trop Dis 4:e614CrossRefPubMedPubMedCentralGoogle Scholar
  19. Hua G, Jurat-Fuentes JL, Adang MJ (2004) Bt-R1a extracellular cadherin repeat 12 mediates Bacillus thuringiensis Cry1Ab binding and cytotoxicity. J Biol Chem 279:28051–28056CrossRefPubMedGoogle Scholar
  20. Hua G, Zhang R, Abdullah MA, Adang MJ (2008) Anopheles gambiae cadherin AgCad1 binds the Cry4Ba toxin of Bacillus thuringiensis israelensis and a fragment of AgCad1 synergizes toxicity. Biochemistry 47:5101–5110CrossRefPubMedPubMedCentralGoogle Scholar
  21. Hui F, Scheib U, Hu Y, Sommer RJ, Aroian RV, Ghosh P (2012) Structure and glycolipid binding properties of the nematicidal protein Cry5B. Biochemistry 51:9911–9921CrossRefPubMedPubMedCentralGoogle Scholar
  22. Jones JT, Haegeman A, Danchin EG, Gaur HS, Helder J, Jones MG, Kikuchi T, Manzanilla-López R, Palomares-Rius JE, Wesemael WM, Perry RN (2013) Top 10 plant-parasitic nematodes in molecular plant pathology. Mol Plant Pathol 14:946–961CrossRefPubMedGoogle Scholar
  23. Keiser J, Utzinger J (2008) Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. JAMA 299:1937–1948CrossRefPubMedGoogle Scholar
  24. Lisa DM, Dino E, Joel SG, Jerald SF, Raffi VA (2000) Bacillus thuringiensis (Bt) toxin susceptibility and isolation of resistance mutants in the nematode Caenorhabditis elegans. Genetics 155:1693–1699Google Scholar
  25. Los FC, Kao CY, Smitham J, McDonald KL, Ha C, Peixoto CA, Aroian RV (2011) RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin. Cell Host Microbe 9:147–157CrossRefPubMedPubMedCentralGoogle Scholar
  26. Pettitt J (2005) The cadherin superfamily (December 29, 2005). In: WormBook. The C. elegans Research Community, WormBook, p 1–9. Online review, http://www.wormbook.org
  27. Pigott CR, Ellar DJ (2007) Role of receptors in Bacillus thuringiensis crystal toxin activity. Microbiol Mol Biol Rev 71:255–281CrossRefPubMedPubMedCentralGoogle Scholar
  28. Rajagopal R, Sivakumar S, Agrawal N, Malhotra P, Bhatnagar RK (2002) Silencing of midgut aminopeptidase N of Spodoptera litura by double-stranded RNA establishes its role as Bacillus thuringiensis toxin receptor. J Biol Chem 277:46849–46851CrossRefPubMedGoogle Scholar
  29. Riga E (2011) The effects of Brassica green manures on plant parasitic and free living nematodes used in combination with reduced rates of synthetic nematicides. J Nematol 43:119–121PubMedPubMedCentralGoogle Scholar
  30. Roh JY, Choi JY, Li MS, Jin BR, Je YH (2007) Bacillus thuringiensis as a specific, safe, and effective tool for insect pest control. J Microbiol Biotechnol 17:547–559PubMedGoogle Scholar
  31. Rosas-Garcia NM (2009) Biopesticide production from Bacillus thuringiensis: an environmentally friendly alternative. Recent Pat Biotechnol 3:28–36CrossRefPubMedGoogle Scholar
  32. Schnepf E, Crickmore N, Van Rie J, Lereclus D, Baum J, Feitelson J, Zeigler DR, Dean DH (1998) Bacillus thuringiensis and its pesticidal crystal proteins. Microbiol Mol Biol Rev 62:775–806PubMedPubMedCentralGoogle Scholar
  33. Vadlamudi RK, Weber E, Ji I, Ji TH, Bulla LA (1995) Cloning and expression of a receptor for an insecticidal toxin of Bacillus thuringiensis. J Biol Chem 270:5490–5494CrossRefPubMedGoogle Scholar
  34. Wei JZ, Hale K, Carta L, Platzer E, Wong C, Fang SC, Aroian RV (2003) Bacillus thuringiensis crystal proteins that target nematodes. Proc Natl Acad Sci U S A 100:2760–2765CrossRefPubMedPubMedCentralGoogle Scholar
  35. Zhang R, Hua G, Andacht TM, Adang MJ (2008) A 106-kDa aminopeptidase is a putative receptor for Bacillus thuringiensis Cry11Ba toxin in the mosquito Anopheles gambiae. Biochemistry 47:11263–11272CrossRefPubMedPubMedCentralGoogle Scholar
  36. Zhang F, Peng D, Ye X, Yu Z, Hu Z, Ruan L, Sun M (2012) In vitro uptake of 140 kDa Bacillus thuringiensis nematicidal crystal proteins by the second stage juvenile of Meloidogyne hapla. PLoS One 7:e38534CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Donghai Peng
    • 1
  • Danfeng Wan
    • 1
  • Chunsheng Cheng
    • 1
  • Xiaobo Ye
    • 1
  • Ming Sun
    • 1
  1. 1.State Key Laboratory of Agricultural Microbiology, College of Life Science and TechnologyHuazhong Agricultural UniversityWuhanPeople’s Republic of China

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