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Science 318 (5856): 1640-1642

Copyright © 2007 by the American Association for the Advancement of Science

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*

Abstract: 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} (A.B.); mario{at} (M.S.)

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Appl. Envir. Microbiol. 79, 6969-6973
   Abstract »    Full Text »    PDF »
A Spodoptera exigua Cadherin Serves as a Putative Receptor for Bacillus thuringiensis Cry1Ca Toxin and Shows Differential Enhancement of Cry1Ca and Cry1Ac Toxicity.
X.-L. Ren, R.-R. Chen, Y. Zhang, Y. Ma, J.-J. Cui, Z.-J. Han, L.-L. Mu, and G.-Q. Li (2013)
Appl. Envir. Microbiol. 79, 5576-5583
   Abstract »    Full Text »    PDF »
Differential Role of Manduca sexta Aminopeptidase-N and Alkaline Phosphatase in the Mode of Action of Cry1Aa, Cry1Ab, and Cry1Ac Toxins from Bacillus thuringiensis.
B. Flores-Escobar, H. Rodriguez-Magadan, A. Bravo, M. Soberon, and I. Gomez (2013)
Appl. Envir. Microbiol. 79, 4543-4550
   Abstract »    Full Text »    PDF »
Sodium Solute Symporter and Cadherin Proteins Act as Bacillus thuringiensis Cry3Ba Toxin Functional Receptors in Tribolium castaneum.
E. Contreras, M. Schoppmeier, M. D. Real, and C. Rausell (2013)
J. Biol. Chem. 288, 18013-18021
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Retargeting of the Bacillus thuringiensis toxin Cyt2Aa against hemipteran insect pests.
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PNAS 110, 8465-8470
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Association of Cry1Ac Toxin Resistance in Helicoverpa zea (Boddie) with Increased Alkaline Phosphatase Levels in the Midgut Lumen.
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Science 337, 85-88
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Parallel Evolution of Bacillus thuringiensis Toxin Resistance in Lepidoptera.
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Communal Benefits of Transgenic Corn.
B. E. Tabashnik (2010)
Science 330, 189-190
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Role of Alkaline Phosphatase from Manduca sexta in the Mechanism of Action of Bacillus thuringiensis Cry1Ab Toxin.
I. Arenas, A. Bravo, M. Soberon, and I. Gomez (2010)
J. Biol. Chem. 285, 12497-12503
   Abstract »    Full Text »    PDF »
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
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Cadherin Fragments from Anopheles gambiae Synergize Bacillus thuringiensis Cry4Ba's Toxicity against Aedes aegypti Larvae.
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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
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Asymmetrical cross-resistance between Bacillus thuringiensis toxins Cry1Ac and Cry2Ab in pink bollworm.
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PNAS 106, 11889-11894
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A Novel Tenebrio molitor Cadherin Is a Functional Receptor for Bacillus thuringiensis Cry3Aa Toxin.
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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.
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Appl. Envir. Microbiol. 75, 3842-3850
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Enhancement of Bacillus thuringiensis Cry3Aa and Cry3Bb Toxicities to Coleopteran Larvae by a Toxin-Binding Fragment of an Insect Cadherin.
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Delaying insect resistance to transgenic crops.
B. E. Tabashnik (2008)
PNAS 105, 19029-19030
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The Molecular Biology Toolbox and Its Use in Basic and Applied Insect Science.
M. Cusson (2008)
BioScience 58, 691-700
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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
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Biotechnological Prospects for Engineering Insect-Resistant Plants.
J. A. Gatehouse (2008)
Plant Physiology 146, 881-887
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PLANT SCIENCE: The Power of the Pyramid.
W. J. Moar and K. J. Anilkumar (2007)
Science 318, 1561-1562
   Abstract »    Full Text »    PDF »

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