Efficacy of genetically modified Bt toxins against insects with different genetic mechanisms of resistance

Abstract

Transgenic crops that produce Bacillus thuringiensis (Bt) toxins are grown widely for pest control, 1 but insect adaptation can reduce their efficacy. [2][3][4][5][6] The genetically modified Bt toxins Cry1AbMod and Cry1AcMod were designed to counter insect resistance to native Bt toxins Cry1Ab and Cry1Ac. 7 Previous results suggested that the modified toxins would be effective only if resistance was linked T A B A S H N I K E T A L ., N A T U R E B I O T E C H N O L O G Y 2 9 : 1 2 ( D E C E M B E R 2 0 1 1 )2 with mutations in genes encoding toxin-binding cadherin proteins. 7 Here we report evidence from five major crop pests refuting this hypothesis. Relative to native toxins, the potency of modified toxins was >350-fold higher against resistant strains of Plutella xylostella and Ostrinia nubilalis in which resistance was not linked with cadherin mutations. Conversely, the modified toxins provided little or no advantage against some resistant strains of three other pests with altered cadherin. Independent of the presence of cadherin mutations, the relative potency of the modified toxins was generally higher against the most resistant strains.The toxins produced by Bt kill some major insect pests but cause little or no harm to people and most other organisms. 8 Bt toxins have been used in sprays for decades and in transgenic plants since 1996 (ref. 6). Transgenic corn and cotton producing Bt toxins were planted on >58 million hectares worldwide in 2010 (ref. 1). The primary threat to the longterm efficacy of Bt toxins is the evolution of resistance by pests. [2][3][4][5][6] Many insects have been selected for resistance to Bt toxins in the laboratory, and some populations of at least eight crop pests have evolved resistance to Bt toxins outside of the laboratory, including two species resistant to Bt sprays and at least six species resistant to Bt crops. [2][3][4][5][6][9][10][11][12][13] The most widely used Bt toxins are crystalline proteins in the Cry1A family, particularly Cry1Ab in transgenic Bt corn and Cry1Ac in transgenic Bt cotton, which kill some lepidopteran larvae. 3 Cry1A toxins bind to the extracellular domains of cadherin, aminopeptidase, and alkaline phosphatase in larval midgut membranes. 14,15 Disruption of Bt toxin binding to midgut receptors is the most common general mechanism of insect resistance. 9 Mutations in the genes encoding midgut cadherins that bind Cry1Ac are linked with resistance in at least three lepidopteran pests of cotton, [16][17][18] but such cadherin mutations are not the primary cause of many other cases of field-and laboratory-selected resistance. 9,19,20 Although some aspects of the mode of action of Bt toxins remain unresolved, extensive evidence shows that after Cry1A protoxins are ingested by larvae, they are solubilized in the gut and cleaved by mid-gut proteases such as trypsin to yield activated 60-kD monomeric toxins that bind with membrane-associated receptors. 14,15 The signaling model suggests that after protease-activated monomeric toxins bind to ca...

A heterozygous moth genome provides insights into herbivory and detoxification

“…Recently, the total cost of damage and management worldwide was estimated at $4-5 billion per annum 5,6 . This insect is the first species to have evolved resistance to dichlorodiphenyltrichloroethane (DDT) in the 1950s 7 and to Bacillus thuringiensis (Bt) toxins in the 1990s 8 and has developed resistance to all classes of insecticide, making it increasingly difficult to control 9,10 . P. xylostella provides an exceptional system for understanding the genetic and molecular bases of how insect herbivores cope with the broad range of plant defenses and chemicals encountered in the environment (Supplementary Fig.…”

The role of biotechnology in agricultural production and food supply

“…GM soybean has made rapid strides in recent decades, and its cultivation area has been increasing yearly. Currently, genetic modification has been successful in maize, tomato, rice and cotton plantations (Sanahuja et al, 2011;Tabashnik et al, 2011), mainly by inserting exogenous genes (transgene) that encode a protein that is toxic to specific pests.…”

Bacillus thuringiensis resistance in Plutella — too many trees?

“…As mentioned above, cadherin is a known receptor for Bt toxins in other insects and mutations in its gene have been found in resistant insects. The observation that a genetically modified form of Cry1A toxin that is believed to by-pass cadherin-based resistance mechanisms [21] could overcome resistance in P. xylostella NO-QAGE [22] initially suggested the involvement of this protein. However genetic mapping studies ruled out the possibility that resistance was due to mutations in cadherin in NO-QA [19] and also in Cry1Ac-R [23].…”