Continuous evolution of B. thuringiensis toxins overcomes insect resistance

The Bacillus thuringiensis δ-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits. The development of insect resistance to Bt toxins endangers their long-term effectiveness. We developed a phage-assisted cont...

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Main Authors:	Badran, Ahmed H., Guzov, Victor M., Huai, Qing, Kemp, Melissa M., Vishwanath, Prashanth, Kain, Wendy, Nance, Autumn M., Evdokimov, Artem, Moshiri, Farhad, Turner, Keith H., Wang, Ping, Malvar, Thomas, Liu, David R.
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865400/

id	pubmed-4865400
recordtype	oai_dc
spelling	pubmed-48654002016-10-27 Continuous evolution of B. thuringiensis toxins overcomes insect resistance Badran, Ahmed H. Guzov, Victor M. Huai, Qing Kemp, Melissa M. Vishwanath, Prashanth Kain, Wendy Nance, Autumn M. Evdokimov, Artem Moshiri, Farhad Turner, Keith H. Wang, Ping Malvar, Thomas Liu, David R. Article The Bacillus thuringiensis δ-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits. The development of insect resistance to Bt toxins endangers their long-term effectiveness. We developed a phage-assisted continuous evolution (PACE) selection that rapidly evolves high-affinity protein-protein interactions, and applied this system to evolve variants of the Bt toxin Cry1Ac that bind a cadherin-like receptor from the insect pest Trichoplusia ni (TnCAD) that is not natively targeted by wild-type Cry1Ac. The resulting evolved Cry1Ac variants bind TnCAD with high affinity (Kd = 11–41 nM), kill TnCAD-expressing insect cells that are not susceptible to wild-type Cry1Ac, and kill Cry1Ac-resistant T. ni insects up to 335-fold more potently than wild-type Cry1Ac. Our findings establish that the evolution of Bt toxins with novel insect cell receptor affinity can overcome Bt toxin resistance in insects and confer lethality approaching that of the wild-type Bt toxin against non-resistant insects. 2016-04-27 2016-05-05 /pmc/articles/PMC4865400/ /pubmed/27120167 http://dx.doi.org/10.1038/nature17938 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Badran, Ahmed H. Guzov, Victor M. Huai, Qing Kemp, Melissa M. Vishwanath, Prashanth Kain, Wendy Nance, Autumn M. Evdokimov, Artem Moshiri, Farhad Turner, Keith H. Wang, Ping Malvar, Thomas Liu, David R.
spellingShingle	Badran, Ahmed H. Guzov, Victor M. Huai, Qing Kemp, Melissa M. Vishwanath, Prashanth Kain, Wendy Nance, Autumn M. Evdokimov, Artem Moshiri, Farhad Turner, Keith H. Wang, Ping Malvar, Thomas Liu, David R. Continuous evolution of B. thuringiensis toxins overcomes insect resistance
author_facet	Badran, Ahmed H. Guzov, Victor M. Huai, Qing Kemp, Melissa M. Vishwanath, Prashanth Kain, Wendy Nance, Autumn M. Evdokimov, Artem Moshiri, Farhad Turner, Keith H. Wang, Ping Malvar, Thomas Liu, David R.
author_sort	Badran, Ahmed H.
title	Continuous evolution of B. thuringiensis toxins overcomes insect resistance
title_short	Continuous evolution of B. thuringiensis toxins overcomes insect resistance
title_full	Continuous evolution of B. thuringiensis toxins overcomes insect resistance
title_fullStr	Continuous evolution of B. thuringiensis toxins overcomes insect resistance
title_full_unstemmed	Continuous evolution of B. thuringiensis toxins overcomes insect resistance
title_sort	continuous evolution of b. thuringiensis toxins overcomes insect resistance
description	The Bacillus thuringiensis δ-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits. The development of insect resistance to Bt toxins endangers their long-term effectiveness. We developed a phage-assisted continuous evolution (PACE) selection that rapidly evolves high-affinity protein-protein interactions, and applied this system to evolve variants of the Bt toxin Cry1Ac that bind a cadherin-like receptor from the insect pest Trichoplusia ni (TnCAD) that is not natively targeted by wild-type Cry1Ac. The resulting evolved Cry1Ac variants bind TnCAD with high affinity (Kd = 11–41 nM), kill TnCAD-expressing insect cells that are not susceptible to wild-type Cry1Ac, and kill Cry1Ac-resistant T. ni insects up to 335-fold more potently than wild-type Cry1Ac. Our findings establish that the evolution of Bt toxins with novel insect cell receptor affinity can overcome Bt toxin resistance in insects and confer lethality approaching that of the wild-type Bt toxin against non-resistant insects.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865400/
_version_	1613578757940969472

Continuous evolution of B. thuringiensis toxins overcomes insect resistance

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