Bacillus thuringiensisinsecticidal three-domain Cry toxins: mode of action, insect resistance and consequences for crop protection

Abstract

Bacillus thuringiensis bacteria are insect pathogens that produce different Cry and Cyt toxins to kill their hosts. Here we review the group of three-domain Cry (3d-Cry) toxins. Expression of these 3d-Cry toxins in transgenic crops has contributed to efficient control of insect pests and a reduction in the use of chemical insecticides. The mode of action of 3d-Cry toxins involves sequential interactions with several insect midgut proteins that facilitate the formation of an oligomeric structure and induce its insertion into the membrane, forming a pore that kills midgut cells. We review recent progress in our understanding of the mechanism of action of these Cry toxins and focus our attention on the different mechanisms of resistance that insects have evolved to counter their action, such as mutations in cadherin, APN and ABC transporter genes. Activity of Cry1AMod toxins, which are able to form toxin oligomers in the absence of receptors, against different resistant populations, including those affected in the ABC transporter and the role of dominant negative mutants as antitoxins, supports the hypothesis that toxin oligomerization is a limiting step in the Cry insecticidal activity. Knowledge of the action of 3d-Cry toxin and the resistance mechanisms to these toxins will set the basis for a rational design of novel toxins to overcome insect resistance, extending the useful lifespan of Cry toxins in insect control programs.

Bringing New Plant Varieties to Market: Plant Breeding and Selection Practices Advance Beneficial Characteristics while Minimizing Unintended Changes

“…In recent years, the trend is to include multiple genes of interest within a single DNA construct (Weber et al, 2012;NAS, 2016). For example, for effective insect control, different mechanisms of action can be identified by a combination of competitive binding experiments and testing new control agents against insects resistant to other insecticides (Pardo-López et al, 2013;Ladics et al, 2015aLadics et al, , 2015bChakroun et al, 2016;Jerga A et al, 2016;Jurat-Fuentes and Crickmore, 2017;Moar et al, 2017). Typically, dozens of versions of an expression cassette are tested in plants, both in greenhouse and confined field trials, to determine which best optimizes the gene expression needed to ensure commercial viability and reproducible efficacy of the trait.…”

Bacillus thuringiensis resistance in Plutella — too many trees?

“…It may be a coincidence that three closely linked genes (encoding ABCC2/3 and MAP4K4) are all involved in the resistance phenotype, alternatively all three may be involved in some form of regulon whose organisation or role is not understood. If there are multiple toxin receptor proteins in Plutella (eg ALP and ABCC2/3) then they could be acting independently, cooperatively, or sequentially as proposed for Manduca sexta [3]. A resistance mechanism driven by perturbations in intracellular regulatory networks has the advantage of being able to explain away a wide range of experimental observations as potentially many stimuli could affect a network and influence susceptibility.…”

“…By far, the most common resistance phenotype is known as "mode 1" in which the insect shows resistance to several Cry1A but not to Cry1C or Cry2A toxins [2], it is this phenotype that will be discussed here. Since the first Bt-resistant insects were identified much research effort has been expended in the search for the underlying genetic, physiological and biochemical mechanisms [3]. For some insects such as Helicoverpa armigera mutations in a known receptor for Bt toxins (cadherin), were found to associate with the resistance phenotype [4].…”

Is there a transgenerational inheritance of host resistance against pathogens? Lessons from the Galleria mellonella-Bacillus thuringiensis interaction model

“…alkaline-phosphatase, amino-peptidase, lipoproteins), resulting in cell intoxication and osmotic lysis. 11,12 Some Cry toxins can kill the insect on their own, as shown in transgenic Bt-crops expressing cry genes. 13 The lethal effect depends on the ingested amount of toxin and the size of the larva.…”

“…In the particular case of resistance to Cry toxins, the reduced susceptibility of the host is often due to alterations of components of the toxin lytic pathway, for example via mutations in the binding sites of the toxin receptor or via the absence of receptor on the surface of intestinal cells. 11 Deregulating genes involved in host defense mechanisms, such as genes encoding antimicrobial peptides, is also a means of becoming resistant to mixtures of Bt Spore-Cry.…”