Delta endotoxins (δ-endotoxins) are a family ofpore-forming toxins produced byBacillus thuringiensis species of bacteria. They are useful for theirinsecticidal action and are the primary toxin produced by the genetically modified (GM)Bt maize/corn and other GM crops. Duringspore formation the bacteria produce crystals of such proteins (hence the nameCry toxins) that are also known asparasporal bodies, next to theendospores; as a result some members are known as aparasporin. TheCyt (cytolytic) toxin group is another group of delta-endotoxins formed in the cytoplasm.VIP toxins (vegetative insecticidal proteins) are formed at other stages of the life cycle.[2]
When an insect ingests these proteins, they are activated byproteolytic cleavage. The N-terminus is cleaved in all of the proteins and aC-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gutepithelium and causescell lysis by the formation ofcation-selective channels, which leads to death.[3][1]
For many years there was no clarity as to the relationship betweenaminopeptidase N and Bt toxins. Although AP-N does bind Cry proteins in vitro[4] (reviewed by Soberón et al. 2009[5] and Pigott & Ellar 2007[6]),[7] no cases ofresistance – or even reduced in vitro binding – due to AP-N structure alteration were known through 2002, and there was some doubt that the resistance mechanism was so straight forward. Indeed, Luo et al. 1997, Mohammed et al. 1996, and Zhu et al. 2000positively found this tonot occur inLepidoptera examples.[4] Subsequently, however Herrero et al. 2005 showed correlation between nonexpression and Bt resistance,[7] and actual resistance was found inHelicoverpa armigera by Zhang et al. 2009,[7][8] inOstrinia nubilalis by Khajuria et al. 2011, and inTrichoplusia ni by Baxter et al. 2011 and Tiewsiri & Wang 2011 (also all Lepidoptera).[7] There continues to be confirmation that AP-Ns do not by themselves affect resistance in some cases, possibly due to sequential binding by the toxin being required to produce its effect. In this sequence each binding step is theoretically not indispensable, but if it occurs does contribute to the final pore formation result.[8]
B. thuringiensis encodes many proteins of the delta endotoxin family (InterPro: IPR038979), with some strains encoding multiple types simultaneously.[9] A gene mostly found onplasmids,[10] delta-entotoxins sometimes show up in genomes of other species, albeit at a lower proportion than those found inB. thuringiensis.[11] The gene names looks likeCry3Bb, which in this case indicates a Cry toxin of superfamily 3 family B subfamily b.[12]
Cry proteins that are interesting to cancer research are listed under a parasporin (PS) nomenclature in addition to the Cry nomenclature. They do not kill insects, but instead kill leukemia cells.[13][14][15] The Cyt toxins tend to form their own group distinct from Cry toxins.[16] Not allCry — crystal-form — toxins directly share a common root.[17] Examples of non-three-domain toxins that nevertheless have aCry name includeCry34/35Ab1 and related beta-sandwich binary (Bin-like) toxins,Cry6Aa, and many beta-sandwich parasporins.[18]
Specific delta-endotoxins that have been inserted withgenetic engineering include Cry3Bb1 found inMON 863 and Cry1Ab found inMON 810, both of which aremaize/corn cultivars. Cry3Bb1 is particularly useful because it kills Coleopteran insects such as thecorn rootworm, an activity not seen in other Cry proteins.[1] Other common toxins includeCry2Ab andCry1F incotton andmaize/corn.[19] In addition,Cry1Ac is effective as a vaccine adjuvant in humans.[20]
Some insects populations have started to develop resistance towards delta endotoxin, with five resistant species found as of 2013. Plants with two kinds of delta endotoxins tend to make resistance happen slower, as the insects have to evolve to overcome both toxins at once. Planting non-Bt plants with the resistant plants will reduce the selection pressure for developing the toxin. Finally, two-toxin plants should not be planted with one-toxin plants, as one-toxin plants act as a stepping stone for adaption in this case.[19]
^abcdGalitsky N, Cody V, Wojtczak A, Ghosh D, Luft JR, Pangborn W, English L (August 2001). "Structure of the insecticidal bacterial delta-endotoxin Cry3Bb1 ofBacillus thuringiensis".Acta Crystallographica. Section D, Biological Crystallography.57 (Pt 8):1101–1109.doi:10.1107/S0907444901008186.PMID11468393.
^Roger Hull; et al. (2021). "Risk assessment and management—Environment".Genetically Modified Plants (second ed.).Upon sporulation,B. thuringiensis forms proteinaceous insecticidal δ-endotoxins either in crystals (Cry toxins) or cytoplasmically (Cyt toxins), which are encoded by cry or cyt genes, respectively. When insects ingest toxin crystals, the enzymes in their digestive tract cause the toxin to become activated. The toxin binds to the insect's gut membranes, forming a pore that results in swelling, cell lysis, and eventually killing the insect.B. thuringiensis also produces insecticidal proteins at other stages in its lifecycle, specifically the vegetative insecticidal proteins (VIPs)
^abGrochulski P, Masson L, Borisova S, Pusztai-Carey M, Schwartz JL, Brousseau R, Cygler M (December 1995). "Bacillus thuringiensis CryIA(a) insecticidal toxin: crystal structure and channel formation".Journal of Molecular Biology.254 (3):447–464.doi:10.1006/jmbi.1995.0630.PMID7490762.
^abTabashnik BE, Brévault T, Carrière Y (June 2013). "Insect resistance to Bt crops: lessons from the first billion acres".Nature Biotechnology.31 (6):510–521.doi:10.1038/nbt.2597.PMID23752438.S2CID205278530.
