Bacillus thuringiensis Cry1A toxins are versatile proteins with multiple modes of action: Two distinct pre-pores are involved in toxicity

Biochemical Journal

Volumn 459, Issue 2, 2014, Pages 383-396

  Gómez, Isabel ^a   Sánchez, Jorge ^a   Muñoz Garay, Carlos ^a   Matus, Violeta ^a   Gill, Sarjeet S ^b   Soberón, Mario ^a   Bravo, Alejandra ^a  

^a INSTITUTO DE BIOTECNOLOGÍA   (Mexico)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Bacillus thuringiensis; Cry toxin; Mechanism of action; Oligomerization; Pore forming toxin; Pre pore

Indexed keywords

CADHERIN; CADHERIN RECEPTOR; CRY1AB TOXIN; CRY1AC TOXIN; MONOMER; OLIGOMER; PROTOXIN; RECEPTOR; TRYPSIN; UNCLASSIFIED DRUG;

ARTICLE; BACILLUS THURINGIENSIS; BACTERIAL STRAIN; BINDING ASSAY; CELL MEMBRANE; CHANNEL GATING; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; HEAT SENSITIVITY; INSECT RESISTANCE; INSECTICIDAL ACTIVITY; LIPID BILAYER; MANDUCA SEXTA; MIDGUT; MOLECULAR WEIGHT; NONHUMAN; OLIGOMERIZATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; WESTERN BLOTTING;

ANIMALS; BACTERIAL PROTEINS; CADHERINS; CELL MEMBRANE; ENDOTOXINS; ENZYME-LINKED IMMUNOSORBENT ASSAY; HEMOLYSIN PROTEINS; MANDUCA; MICROVILLI; PROTEIN BINDING; RECEPTORS, CELL SURFACE; TRYPSIN;

EID: 84897546370     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20131408     Document Type: Article

References (69)

1. González, M. R., Bischofberger, M., Pernot, L., van der Goot, F. G. and Freche, B. (2008) Bacterial pore-forming toxins: the (w)hole story? Cell. Mol. Life Sci. 65, 493-507
2. Bischofberger, M., Iacovache, I. and van der Goot, F. G. (2012) Pathogenic pore-forming proteins: function and host response. Cell Host Microbe 12, 266-275
3. Dunkelberger, J. R. and Song, W.-C. (2010) Complement and its role in innate and adaptive immune responses. Cell Res. 20, 34-50
4. de Maagd, R. A., Bravo, A., Berry, C., Crickmore, N. and Schnepf, H. E. (2003) Structure, diversity and evolution of protein toxins from spore-forming entomopathogenic bacteria. Annu. Rev. Genet. 37, 409-433 (Pubitemid 38041433)
5. Reference deleted
6. James, C. (2012) Global Status of Commercialized Biotech/GM Crops: 2012 (ISAAA Brief No. 44), ISAAA, Ithaca, NY
7. Qaim, M. and Zilberman, D. (2003) Yield effects of genetically modified crops in developing countries. Science 299, 900-902 (Pubitemid 36182450)
8. Pacheco, S., Gómez, I., Arenas, I., Saab-Rincon, G., Rodríguez-Almazán, C., Gill, S. S., Bravo, A. and Soberón, M. (2009) Domain II loop 3 of Bacillus thuringiensis Cry1Ab toxin is involved in a "ping pong" binding mechanism with Manduca sexta aminopeptidase-N and cadherin receptors. J. Biol. Chem. 284, 32750-32757
9. Arenas, I., Bravo, A., Soberón, M. and Gómez, I. (2010) Role of alkaline phosphatase from Manduca sexta in the mechanism of action of Bacillus thuringiensis Cry1Ab toxin. J. Biol. Chem. 285, 12497-12503
10. Gómez, I., Dean, D. H., Bravo, A. and Soberón, M. (2003) Molecular basis for Bacillus thuringiensis Cry1Ab toxin specificity: two structural determinants in the Manduca sexta Bt-R1 receptor interact with loops α-8 and 2 in domain II of Cy1Ab toxin. Biochemistry 42, 10482-10489
11. Gómez, I., Arenas, I., Benitez, I., Miranda-Ríos, J., Becerril, B., Grande, R., Almagro, J. C., Bravo, A. and Soberón, M. (2006) Specific epitopes of domains II and III of Bacillus thuringiensis Cry1Ab toxin involved in the sequential interaction with cadherin and aminopeptidase-N receptors in Manduca sexta. J. Biol. Chem. 281, 34032-34039
12. Bravo, A., Gómez, I., Conde, J., Muñoz-Garay, C., Sánchez, J., Miranda, R., Zhuang, M., Gill, S. S. and Soberón, 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, 38-46 (Pubitemid 39463332)
13. Gómez, I., Sánchez, J., Miranda, R., Bravo, A. and Soberón, M. (2002) Cadherin-like receptor binding facilitates proteolytic cleavage of helix α-1 in domain I and oligomer pre-pore formation of Bacillus thuringiensis Cry1Ab toxin. FEBS Lett. 513, 242-246
14. Vachon, V., Laprade, R. and Schwartz, J. L. (2012) Current models of the mode of action of Bacillus thuringiensis insecticidal crystal proteins: a critical review. J. Invertebr. Pathol. 111, 1-12
15. Smedley, D. P., Armstrong, G. and Ellar, D. J. (1997) Channel activity caused by Bacillus thuringiensis δ-endotoxin preparation depends on the method of activation. Mol. Membr. Biol. 14, 13-18 (Pubitemid 27219902)
16. Rausell, C., Muñoz-Garay, C., Miranda-CassoLuengo, R., Gómez, I., Rudiño-Piñera, E., Soberón, M. and Bravo, A. (2004) Tryptophan spectroscopy studies and black lipid bilayer analysis indicate that the oligomeric structure of Cry1Ab toxin from Bacillus thuringiensis is the membrane-insertion intermediate. Biochemistry 43, 166-174 (Pubitemid 38055952)
17. Schwartz, J. L., Lu, Y. J., Söhnlein, P., Brousseau, R., Laprade, R., Masson, L. and Adang, M. J. (1997) Ion channels formed in planar lipid bilayers by Bacillus thuringiensis toxins in the presence of Manduca sexta midgut receptors. FEBS Lett. 412, 270-276 (Pubitemid 27321264)
18. Schwartz, J. L., Potvin, L., Chen, X. J., Brousseau, R., Laprade, R. and Dean, D. H. (1997) Single-site mutations in the conserved alternating-arginine region affect ionic channels formed by CryIAa, a Bacillus thuringiensis toxin. Appl. Environ. Microbiol. 63, 3978-3984 (Pubitemid 27411357)
19. Schwartz, J. L., Garneau, L., Savaria, D., Masson, L., Brousseau, R. and Rousseau, E. (1993) Lepidopteran specific crystal toxins from Bacillus thuringiensis form cation and anion selective channels in planar lipid bilayers. J. Membr. Biol. 132, 53-62 (Pubitemid 23071926)
20. Peyronnet, O., Vachon, V., Schwartz, J. L. and Laprade, R. (2001) Ion channels in planar lipid bilayers by the Bacillus thuringiensis toxin Cry1Aa in the presence of gypsy moth (Lymantria dispar) brush border membrane. J. Membr. Biol. 184, 45-54 (Pubitemid 33016170)
21. Putheeranurak, T., Uawithya, P., Potvin, L., Angsuthanasombat, Ch. and Schwartz, J. L. (2004) Ion channels in planar lipid bilayers by the dipteran specific Cry4B Bacillus thuringiensis toxins and its α1-α5 fragment. Mol. Membr. Biol. 21, 67-74 (Pubitemid 38129277)
22. Masson, L., Tabashnik, B. E., Mazza, A., Prefontaine, G., Potvin, L., Borusseau, R. and Schwartz, J. L. (2002) Mutagenic analysis of a conserved region of domain III in the Cry1Aa toxin of Bacillus thuringiensis. Appl. Environ. Microbiol. 68, 194-200 (Pubitemid 34031180)
23. Masson, L., Tabashnik, B. E., Liu, Y.-B., Brousseau, R. and Schwartz, J. L. (1999) Helix 4 of the Bacillus thuringiensis Cry1Aa toxin lines the lumen of the ion cannel. J. Biol. Chem. 274, 31996-32000
24. 2+ release from intracellular stores in Cf1 cells (Choristoneura fumiferana, Lepidoptera). J. Exp. Biol. 201, 1851-1858
25. Rodriguez-Almazán, C., Zavala, L. E., Muñoz-Garay, C., Jimenez-Juarez, N., Pacheco, S., Masson, L., Soberón, M. and Bravo, A. (2009) Dominant negative mutants of Bacillus thuringiensis Cry1Ab toxin function as anti-toxin: demonstration of the role of oligomerization in toxicity. PLoS ONE 5, e5545
26. Jiménez-Juárez, N., Muñoz-Garay, C., Gómez, I., Saab-Rincon, G., Damian-Almazo, J. Y., Gill, S. S., Soberón, M. and Bravo, A. (2007) Bacillus thuringiensis Cry1Ab mutants affecting oligomer formation are non toxic to Manduca sexta larvae. J. Biol. Chem. 282, 21222-21229 (Pubitemid 47099915)
27. Muñoz-Garay, C., Portugal, L., Pardo-López, L., Jiménez-Juárez, N., Arenas, I., Gómez, I., Sanchez-López, R., Arroyo, R., Holzenburg, A., Savva, C. G. et al. (2009) Characterization of the mechanism of action of the genetically modified Cry1AbMod toxin, that is active against Cry1Ab-resistant insects. Biochim. Biophys. Acta Biomembr. 1788, 2229-2237
28. Rajamohan, F., Alcantara, E., Lee, M. K., Chen, X. J., Curtiss, A. and Dean, D. H. (1995) Single amino acid changes in domain II of Bacillus thuringiensis Cry1Ab δ-endotoxin affect irreversible binding to Manduca sexta midgut membrane vesicles. J. Bacteriol. 177, 2276-2282
29. Soberón, M., Pardo-López, L., López, I., Gómez, I., Tabashnik, B. E. and Bravo, A. (2007) Engineering modified Bt toxins to counter insect resistance. Science 318, 1640-1642 (Pubitemid 350233665)
30. Thomas, W. E. and Ellar, D. J. (1983) Bacillus thuringiensis var israelensis crystal δ-endotoxin: effects on insect and mammalian cells in vitro and in vivo. J. Cell Sci. 60, 181-197 (Pubitemid 13090347)
31. Flores-Escobar, B., Rodríguez-Magadan, H., Bravo, A., Soberón, M. and Gómez, I. (2013) Manduca sexta aminopeptidase-N and alkaline phosphatase have a differential role in the mode of action of Cry1Aa, Cry1Ab and Cry1Ac toxins from Bacillus thuringiensis. Appl. Environ. Microbiol. 79, 4543-4550
32. Miranda, R., Zamudio, F. and Bravo, A. (2001) Processing of Cry1Ab δ-endotoxin from Bacillus thuringiensis by midgut proteases: role in toxin activation and inactivation. Insect Biochem. Mol. Biol. 31, 1155-1163 (Pubitemid 33032525)
33. Pérez, C., Muñoz-Garay, C., Portugal, L., Sánchez, J., Gill, S. S., Soberón, M. and Bravo, A. (2007) Bacillus thuringiensis ssp. israelensis Cyt1Aa enhances activity of Cry11Aa toxin by facilitating the formation of a pre-pore oligomeric structure. Cell. Microbiol. 9, 2931-2937 (Pubitemid 350066576)
34. Wolfersberger, M. G. (1993) Preparation and partial characterization of amino acid transporting brush border membrane vesicles from the larval midgut of the gypsy moth (Lymantria dispar) . Arch. Insect Biochem. Physiol. 24, 139-147
35. Gómez, I., Oltean, D. I., Gill, S. S., Bravo, A. and Soberón, M. (2001) Mapping the epitope in cadherin-like receptors involved in Bacillus thuringiensis Cry1A toxin interaction using phage display. J. Biol. Chem. 276, 28906-28912
36. Müeller, P., Rudin, D. O., Tien, H. T. and Westcott, W. C. (1962) Reconstitution of cell membrane structure in vitro and its transformation into an excitable system. Nature 194, 979-980
37. Fabrick, J. A. and Tabashnik, B. E. (2006) Binding of Bacillus thuringiensis toxin Cry1Ac to multiple sites of cadherin in pink bollworm. Insect Biochem. Mol. Biol. 37, 97-100
38. Jenkins, J. L., Lee, M. K., Valaitis, A. P., Curtiss, A. and Dean, D. H. (2000) Bivalent sequential binding model of a Bacillus thuringiensis toxin to gypsy moth aminopeptidase N receptor. J. Biol. Chem. 275, 14423-14431 (Pubitemid 30339728)
39. Tabashnik, B. E., Huang, F., Ghimire, M. N., Leonard, B. R., Siegfried, B. D., Rangasamy, M., Yang, Y., Wy, Y., Gahan, L. J., Heckel, D. G. et al. (2011) Efficacy of genetically modified Bt toxins against insects with different mechanisms of resistance. Nat. Biotechnol. 29, 1128-1131
40. Franklin, M. T., Nieman, C. L., Janmaat, A. F., Soberón, M., Bravo, A., Tabashnik, B. E. and Myers, J. H. (2009) Modified Bacillus thuringiensis toxins and B. thuringiensis aizawai counter green-house-selected resistance in Trichoplusia ni (Lepidoptera: Noctuidae). Appl. Environ. Microbiol. 75, 5739-5741
41. Martin, F. G. and Wolfersberger, M. G. (1995) Bacillus thuringiensis δ-endotoxin and larval Manduca sexta midgut brush border membrane vesicles act synergistically to cause very large increase in the conductance of planar lipid bilayer. J. Exp. Biol. 198, 91-96
42. Lorence, A., Darszon, A., Díaz, C., Liévano, A., Quintero, R. and Bravo, A. (1995) δ-Endotoxins induce cation channels in Spodoptera frugiperda brush border membranes in suspension and in planar lipid bilayers. FEBS Lett. 360, 217-222
43. 2O from phospholipid vesicles is catalyzed by reconstituted midgut membrane. Insect Biochem. 21, 177-184
44. + efflux in vitro. J. Biol. Chem. 269, 10088-10092
45. Obata, F., Kitami, M., Inoue, Y., Atsumi, S., Yoshizawa, Y. and Sato, R. (2009) Analysis of the region for receptor binding and triggering of oligomerization on Bacillus thuringiensis Cry1Aa toxin. FEBS J. 276, 5949-5959
46. Aronson, A. I., Geng, C. and Wu, L. (1999) Aggregation of Bacillus thuringiensis Cry1A toxins upon binding to target insect larval midgut vesicles. Appl. Environ. Microbiol. 65, 2503-2507
47. Ihara, H. and Himeno, M. (2008) Study of the irreversible binding of Bacillus thuringiensis Cry1Aa to brush border membrane vesicles from Bombyx mori midgut. J. Invertebr. Pathol. 98, 177-183
48. 135, is involved in the oligomerization of Cry1Ac1 and Cry1Ab5 Bacillus thuringiensis toxins. Appl. Environ. Microbiol. 67, 5715-5720
49. Muñoz-Garay, C., Sánchez, J., Darszon, A., de Maagd, R. A., Bakker, P., Soberón, M. and Bravo, A. (2006) Permeability changes of Manduca sexta midgut brush border membranes induced by oligomeric structures of different Cry toxins. J. Membr. Biol. 212, 61-68 (Pubitemid 46122154)
50. Xiang, W. F., Qiu, X. L., Zhi, D. X., Min, Z. X., Yuan, L. and Quan, Y. Z. (2009) N546 in β18-β19 loop is important for binding and toxicity of the Bacillus thuringiensis Cry1Ac toxin. J. Invertebr. Pathol. 101, 119-123
51. Chen, J., Hua, G., Jurat-Fuentes, J. L., Abdullah, M. A. and Adang, M. J. (2007) Synergism of Bacillus thuringiensis toxins by a fragment of a toxin-binding cadherin. Proc. Natl. Acad. Sci. U.S.A. 104, 13901-13906 (Pubitemid 350003310)
52. Abdullah, M. A., Moussa, S., Taylor, M. D. and Adang, M. J. (2009) Manduca sexta (Lepidoptera: Sphingidae) cadherin fragments function as synergists for Cry1A and Cry1C Bacillus thuringiensis toxins against noctuid moths Helicoverpa zea, Agrotis ipsilon and Spodoptera exigua. Pest Manag. Sci. 65, 1097-1103
53. Pacheco, S., Gomez, I., Gill, S. S., Bravo, A. and Soberón, M. (2009) Enhancement of insecticidal activity of Bacillus thuringiensis Cry1A toxins by fragments of a toxin-binding cadherin correlates with oligomer formation. Peptides 30, 583-588
54. Park, Y., Hua, G., Abdullah, M. A., Rahman, K. and Adang, M. J. (2009) Cadherin fragments from Anopheles gambiae synergize Bacillus thuringiensis Cry4Ba toxicity against Aedes aegypti larvae. Appl. Environ. Microbiol. 75, 7280-7282
55. Park, Y., Abdullah, M. A., Taylor, M. D., Rahman, K. and Adang, M. J. (2009) Enhancement of Bacillus thuringiensis Cry3Aa and Cry3Bb toxicities to coleopteran larvae by a toxin-binding fragment of an insect cadherin. Appl. Environ. Microbiol. 75, 3086-3092
56. Rodríguez-Almazán, C., Reyes, E. Z., Zuñiga- Navarrete, F., Muñoz-Garay, C., Gómez, I., Evans, A. M., Likitvivatanavong, S., Bravo, A., Gill, S. S. and Soberón, M. (2012) Cadherin binding is not a limiting step for Bacillus thuringiensis subs. israelensis Cry4Ba toxicity to Aedes aegypti larvae. Biochem. J. 443, 711-717
57. 183 in α5 is essential for oligomerization and toxicity of the Bacillus thuringiensis Cry4Ba toxin. Arch. Biochem. Biophys. 445, 46-55
58. Boonserm, P., Davis, P., Ellar, D. J. and Li, J. (2005) Crystal structure of the mosquito-larvicidal toxin Cry4Ba and its biological implications. J. Mol. Biol. 348, 363-382 (Pubitemid 40462102)
59. Hui, F., Scheib, U., Hu, Y., Sommer, R. J., Aroian, R. V. and Ghosh, P. (2012) Structure and glycolipid binding properties of the nematicidal protein Cry5B. Biochemistry 51, 9911-9921
60. Van Rie, J., Jansen, S., Höfte, H., Degheele, D. and Van Mellaert, H. (1989) Specificity of Bacillus thuringiensis δ-endotoxins: importance of specific receptor on the brush border membrane of the midgut of target insects. Eur. J. Biochem. 186, 239-247 (Pubitemid 20015150)
61. Nair, M. S., Liu, X. S. and Dean, D. H. (2008) Membrane insertion of the Bacillus thuringiensis Cry1Ab toxin: single mutation in domain II block partitioning of the toxin into brush border membrane. Biochemistry 47, 5814-5822 (Pubitemid 351747060)
62. Pardo-López, L., Gómez, I., Rausell, C., Sánchez, J., Soberón, M. and Bravo, A. (2006) Structural changes of the Cry1Ac oligomeric pre-pore from Bacillus thuringiensis induced by N-acetylgalactosamine facilitates toxin membrane insertion. Biochemistry 45, 10329-10336 (Pubitemid 44384808)
63. Heckel, D. G. (2012) Learning the ABCs of Bt: ABC transporters and insect resistance to Bacillus thuringiensis provide clues to a crucial step in toxin mode of action. Pestic. Biochem. Physiol. 104, 103-110
64. Zhang, X., Candas, M., Grinko, N. B., Taussig, R. and Bulla, L. A. (2006) A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis. Proc. Natl. Acad. Sci. U.S.A. 103, 9897-9902 (Pubitemid 43993594)
65. Zhang, H., Wu, S., Yang, Y., Tabashnik, B. E. and Wu, Y. (2012) Non-recessive Bt toxin resistance conferred by an intracellular cadherin mutation in field-selected populations of cotton. PLoS ONE 7, e53418
66. Xu, X., Yu, L. and Wu, Y. (2005) Disruption of a cadherin gene associated with resistance to Cry1Ac δ-endotoxin of Bacillus thuringiensis in Helicoverpa armigera. Appl. Environ. Microbiol. 71, 948-954 (Pubitemid 40223583)
67. Anilkumar, K. J., Rodrigo-Simón, A., Ferré, J., Pusztai-Carey, M., Sivasupramaniam, S. and Moar, W. (2008) Production and characterization of Bacillus thuringiensis Cry1Ac-resistant cotton bollworm Helicoverpa zea (Boddie). Appl. Environ. Microbiol. 74, 462-469
68. Caccia, S., Moar, W. J., Chandrashekhar, J., Oppert, C., Anilkumar, K. J., Jurat-Fuentes, J. L. and Ferré, J. (2012) Association of Cry1Ac toxin resistance in Helicoverpa zea (Boddie) with increased alkaline phosphatase levels in midgut lumen. Appl. Environ. Microbiol. 78, 5609-5698
69. Iacovache, I., Degiacomi, M. T., Pernot, L., Ho, S., Schiltz, M., DalPeraro, M. and van der Goot, F. G. (2011) Dual chaperone role of the C-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin. PLoS Pathog. 7, e1002135