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Originally published in Science Express on 1 November 2007
Science 7 December 2007:
Vol. 318. no. 5856, pp. 1640 - 1642
DOI: 10.1126/science.1146453
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Reports

Engineering Modified Bt Toxins to Counter Insect Resistance

Mario Soberón,1* Liliana Pardo-López,1 Idalia López,1 Isabel Gómez,1 Bruce E. Tabashnik,2 Alejandra Bravo1*

The evolution of insect resistance threatens the effectiveness of Bacillus thuringiensis (Bt) toxins that are widely used in sprays and transgenic crops. Resistance to Bt toxins in some insects is linked with mutations that disrupt a toxin-binding cadherin protein. We show that susceptibility to the Bt toxin Cry1Ab was reduced by cadherin gene silencing with RNA interference in Manduca sexta, confirming cadherin's role in Bt toxicity. Native Cry1A toxins required cadherin to form oligomers, but modified Cry1A toxins lacking one {alpha}-helix did not. The modified toxins killed cadherin-silenced M. sexta and Bt-resistant Pectinophora gossypiella that had cadherin deletion mutations. Our findings suggest that cadherin promotes Bt toxicity by facilitating toxin oligomerization and demonstrate that the modified Bt toxins may be useful against pests resistant to standard Bt toxins.

1 Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico.
2 Department of Entomology, University of Arizona, Tucson, AZ, USA.

* To whom correspondence should be addressed. E-mail: bravo{at}ibt.unam.mx (A.B.); mario{at}ibt.unam.mx (M.S.)

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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.
S. Pacheco, I. Gomez, I. Arenas, G. Saab-Rincon, C. Rodriguez-Almazan, S. S. Gill, A. Bravo, and M. Soberon (2009)
J. Biol. Chem. 284, 32750-32757
   Abstract »    Full Text »    PDF »
Cadherin Fragments from Anopheles gambiae Synergize Bacillus thuringiensis Cry4Ba's Toxicity against Aedes aegypti Larvae.
Y. Park, G. Hua, M. A. F. Abdullah, K. Rahman, and M. J. Adang (2009)
Appl. Envir. Microbiol. 75, 7280-7282
   Abstract »    Full Text »    PDF »
Modified Bacillus thuringiensis Toxins and a Hybrid B. thuringiensis Strain Counter Greenhouse-Selected Resistance in Trichoplusia ni.
M. T. Franklin, C. L. Nieman, A. F. Janmaat, M. Soberon, A. Bravo, B. E. Tabashnik, and J. H. Myers (2009)
Appl. Envir. Microbiol. 75, 5739-5741
   Abstract »    Full Text »    PDF »
From the Cover: Asymmetrical cross-resistance between Bacillus thuringiensis toxins Cry1Ac and Cry2Ab in pink bollworm.
B. E. Tabashnik, G. C. Unnithan, L. Masson, D. W. Crowder, X. Li, and Y. Carriere (2009)
PNAS 106, 11889-11894
   Abstract »    Full Text »    PDF »
A Novel Tenebrio molitor Cadherin Is a Functional Receptor for Bacillus thuringiensis Cry3Aa Toxin.
J. Fabrick, C. Oppert, M. D. Lorenzen, K. Morris, B. Oppert, and J. L. Jurat-Fuentes (2009)
J. Biol. Chem. 284, 18401-18410
   Abstract »    Full Text »    PDF »
Mutations in Domain I Interhelical Loops Affect the Rate of Pore Formation by the Bacillus thuringiensis Cry1Aa Toxin in Insect Midgut Brush Border Membrane Vesicles.
G. Lebel, V. Vachon, G. Prefontaine, F. Girard, L. Masson, M. Juteau, A. Bah, G. Larouche, C. Vincent, R. Laprade, et al. (2009)
Appl. Envir. Microbiol. 75, 3842-3850
   Abstract »    Full Text »    PDF »
Enhancement of Bacillus thuringiensis Cry3Aa and Cry3Bb Toxicities to Coleopteran Larvae by a Toxin-Binding Fragment of an Insect Cadherin.
Y. Park, M. A. F. Abdullah, M. D. Taylor, K. Rahman, and M. J. Adang (2009)
Appl. Envir. Microbiol. 75, 3086-3092
   Abstract »    Full Text »    PDF »
Delaying insect resistance to transgenic crops.
B. E. Tabashnik (2008)
PNAS 105, 19029-19030
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The Outlook for Protein Engineering in Crop Improvement.
A. G. Rao (2008)
Plant Physiology 147, 6-12
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Bacillus thuringiensis Cry1Ac Toxin-Binding and Pore-Forming Activity in Brush Border Membrane Vesicles Prepared from Anterior and Posterior Midgut Regions of Lepidopteran Larvae.
A. Rodrigo-Simon, S. Caccia, and J. Ferre (2008)
Appl. Envir. Microbiol. 74, 1710-1716
   Abstract »    Full Text »    PDF »
Biotechnological Prospects for Engineering Insect-Resistant Plants.
J. A. Gatehouse (2008)
Plant Physiology 146, 881-887
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