Bacillus thuringiensis#Insect resistance

In 1902, B. thuringiensis was first discovered in silkworms by Japanese sericultural engineer {{nihongo|Ishiwatari Shigetane|石渡 繁胤}}. He named it B. sotto,{{cite book|title=New Innovative Pesticides|url=https://books.google.com/books?id=ZR3uH7O713QC&pg=PA61|year=1977|publisher=EPA|page=61|quote= In 1915 the bacterium was re-examined and named Bacillus sotto. [...] At about the same time, Beriner was isolating the organism}} using the Japanese word {{nihongo||卒倒|sottō|'collapse'}}, here referring to bacillary paralysis.{{cite book|title=Natural Enemies in the Pacific Area: Biological Control|url=https://books.google.com/books?id=ynweAQAAMAAJ|year=1967|publisher=Fukuoka Entomological Society|page=99|quote= "Sotto" in Japanese means "sudden collapse" or "fainting", and "sotto" of Bacillus thuringiensis var. sotto derives its name from the "sotto" disease.}} In 1911, German microbiologist Ernst Berliner rediscovered it when he isolated it as the cause of a disease called {{lang|de|Schlaffsucht}} in flour moth caterpillars in Thuringia (hence the specific name thuringiensis, "Thuringian").{{cite book | vauthors = Reardon RC, Dubois NR, McLane W |title=Bacillus thuringiensis for managing gypsy moth: a review |url= https://archive.org/details/CAT10861975 |year=1994 | work = USDA Forest Service | publisher = United States Department of Agriculture |quote= Mediterranean flour moths, Ephestia (=Anagasta) kuehniella (Zeller), that were found in stored grain in Thuringia}} B. sotto would later be reassigned as B. thuringiensis var. sotto.{{cite book| vauthors =Steinhaus E |title=Insect Pathology: An Advanced Treatise|url=https://books.google.com/books?id=qXy7rpkMJdwC&pg=PA32|year=2012|publisher=Elsevier|isbn=978-0-323-14317-2|page=32 | quote= Bacillus sotto {{small|Ishiwata}} [→] Taxonomic reassignment: Bacillus thuringiensis var. sotto {{small|Ishiwata}}. [Heimpel and Angus, 1960]}}

In 1976, Robert A. Zakharyan reported the presence of a plasmid in a strain of B. thuringiensis and suggested the plasmid's involvement in endospore and crystal formation.{{cite journal | vauthors = Zakharyan RA, Israelyan YK, Agabalyan AS, Tatevosyan PE, Akopyan S, Afrikyan EK |year=1979 |title=Plasmid DNA from Bacillus thuringiensis |journal=Microbiologiya |volume=48 |issue=2 |pages=226–229 |issn=0026-3656}}{{cite book | veditors = Cheng TC |year=1984 |title=Pathogens of invertebrates: application in biological control and transmission mechanisms |isbn=978-0-306-41700-9 |page=[https://archive.org/details/pathogensofinver07chen/page/159 159] |url-access=registration |url=https://archive.org/details/pathogensofinver07chen/page/159 }} B. thuringiensis is closely related to B. cereus, a soil bacterium, and B. anthracis, the cause of anthrax; the three organisms differ mainly in their plasmids.{{cite book | vauthors = Økstad OA, Kolstø A | title=Genomics of Foodborne Bacterial Pathogens | chapter=Genomics of Bacillus Species | author2-link=Anne-Brit Kolstø | veditors = Wiedmann M, Zhang W | pages= 29–53 | publisher = Springer Science+Business Media, LLC | year = 2011 | doi = 10.1007/978-1-4419-7686-4_2 | isbn= 978-1-4419-7685-7 }}{{rp|34–35}} Like other members of the genus, all three are capable of producing endospores.

B. thuringiensis is placed in the Bacillus cereus group which is variously defined as: seven closely related species: B. cereus sensu stricto (B. cereus), B. anthracis, B. thuringiensis, B. mycoides, B. pseudomycoides, and B. cytotoxicus;{{cite journal | vauthors = Guinebretière MH, Auger S, Galleron N, Contzen M, De Sarrau B, De Buyser ML, Lamberet G, Fagerlund A, Granum PE, Lereclus D, De Vos P, Nguyen-The C, Sorokin A | display-authors = 6 | title = Bacillus cytotoxicus sp. nov. is a novel thermotolerant species of the Bacillus cereus Group occasionally associated with food poisoning | journal = International Journal of Systematic and Evolutionary Microbiology | volume = 63 | issue = Pt 1 | pages = 31–40 | date = January 2013 | pmid = 22328607 | doi = 10.1099/ijs.0.030627-0 | s2cid = 2407509 }} or as six species in a Bacillus cereus sensu lato: B. weihenstephanensis, B. mycoides, B. pseudomycoides, B. cereus, B. thuringiensis, and B. anthracis. Within this grouping B.t. is more closely related to B.ce. It is more distantly related to B.w., B.m., B.p., and B.cy.{{cite journal | vauthors = Kolstø AB, Tourasse NJ, Økstad OA | title = What sets Bacillus anthracis apart from other Bacillus species? | journal = Annual Review of Microbiology | volume = 63 | issue = 1 | pages = 451–476 | year = 2009 | pmid = 19514852 | doi = 10.1146/annurev.micro.091208.073255 | publisher = Annual Reviews | author1-link = Anne-Brit Kolstø }}

There are several dozen recognized subspecies of B. thuringiensis. Subspecies commonly used as insecticides include B. thuringiensis subspecies kurstaki (Btk), subspecies israelensis (Bti) and {{visible anchor|aizawa|text=subspecies aizawai}} (Bta).{{Cite web|last=US EPA|first=OCSPP|date=2016-07-05|title=Bti for Mosquito Control|url=https://www.epa.gov/mosquitocontrol/bti-mosquito-control|access-date=2021-05-10|website=US EPA|language=en}}{{cite web|title=Information on Bacillus thuringiensis subspecies kurstaki (Btk) Excerpts from a Forestry Technical Manual produced by Valent BioSciences, manufacturers of Foray® and DiPel®, two formulations of commercially produced Bacillus thuringiensis var. kurstaki (Btk)|url=https://www.fs.usda.gov/Internet/FSE_DOCUMENTS/fsbdev7_015300.pdf|website=Fs.usda.gov|access-date=2022-04-09}}{{cite web|title=Commonly Asked Questions About Btk (Bacillus thuringiensis var. kurstaki) | vauthors = Ellis JA | work = Department of Entomology, Purdue University |url= https://www2.illinois.gov/sites/agr/Insects/Pests/Documents/GMquestions%20on%20%20Btk.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://www2.illinois.gov/sites/agr/Insects/Pests/Documents/GMquestions%20on%20%20Btk.pdf |archive-date=2022-10-09 |url-status=live |access-date=2022-04-09}}{{cite web|title=Bacillus thuringiensis aizawai strain NB200 (006494) Fact sheet|url=https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-006494_10-Jun-05.pdf |archive-url=https://web.archive.org/web/20170120233800/https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-006494_10-Jun-05.pdf |archive-date=2017-01-20 |url-status=live|website=3.epa.gov|access-date=2022-04-09}} Some Bti lineages are clonal.

Some strains are known to carry the same genes that produce enterotoxins in B. cereus, and so it is possible that the entire B. cereus sensu lato group may have the potential to be enteropathogens.

The proteins that B. thuringiensis is most known for are encoded by cry genes. In most strains of B. thuringiensis, these genes are located on a plasmid (in other words cry is not a chromosomal gene in most strains).{{cite journal | vauthors = Dean DH | title = Biochemical genetics of the bacterial insect-control agent Bacillus thuringiensis: basic principles and prospects for genetic engineering | journal = Biotechnology & Genetic Engineering Reviews | volume = 2 | pages = 341–363 | year = 1984 | pmid = 6443645 | doi = 10.1080/02648725.1984.10647804 | doi-access = free }}{{cite journal |doi=10.4039/Ent124587-4 |title=Invitation Paper (C.p. Alexander Fund): History Of bacillus Thuringiensis berliner Research and Development |year=1992 | vauthors = Beegle CC, Yamamoto T | journal=The Canadian Entomologist |volume=124 |issue=4 |pages=587–616|s2cid=86763021 }}{{cite journal | vauthors = Xu J, Liu Q, Yin X, Zhu S |year=2006|title=A review of recent development of Bacillus thuringiensis ICP genetically engineered microbes |url=http://en.cnki.com.cn/Article_en/CJFDTOTAL-HDKC200601013.htm |journal=Entomological Journal of East China |issue=1 |pages=53–8 |volume=15}} If these plasmids are lost it becomes indistinguishable from B. cereus as B. thuringiensis has no other species characteristics. Plasmid exchange has been observed both naturally and experimentally both within B.t. and between B.t. and two congeners, B. cereus and B. mycoides.

plcR is an indispensable transcription regulator of most virulence factors, its absence greatly reducing virulence and toxicity. Some strains do naturally complete their life cycle with an inactivated plcR. It is half of a two-gene operon along with the heptapeptide {{visible anchor|papR}}. papR is part of quorum sensing in B. thuringiensis.

Various strains including Btk ATCC 33679 carry plasmids belonging to the wider pXO1-like family. (The pXO1 family being a B. cereus-common family with members of ≈330kb length. They differ from pXO1 by replacement of the pXO1 pathogenicity island.) The insect parasite Btk HD73 carries a pXO2-like plasmid (pBT9727) lacking the 35kb pathogenicity island of pXO2 itself, and in fact having no identifiable virulence factors. (The pXO2 family does not have replacement of the pathogenicity island, instead simply lacking that part of pXO2.)

The genomes of the B. cereus group may contain two types of introns, dubbed group I and group II. B.t strains have variously 0–5 group Is and 0–13 group IIs.

There is still insufficient information to determine whether chromosome-plasmid coevolution to enable adaptation to particular environmental niches has occurred or is even possible.

Common with B. cereus but so far not found elsewhere – including in other members of the species group – are the efflux pump BC3663, the N-acyl-L-amino-acid amidohydrolase BC3664, and the methyl-accepting chemotaxis protein BC5034.

It has a similar proteome diversity to its close relative B. cereus.

Into the BT Cotton protein is 'Crystal protein'.

Upon sporulation, B. thuringiensis forms crystals of two types of proteinaceous insecticidal delta endotoxins (δ-endotoxins) called crystal proteins or Cry proteins, which are encoded by cry genes, and Cyt proteins.{{cite web | vauthors = Circkmore N |url= http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/index.html |title=Bacillus thuringiensis toxin nomenclature |access-date=2008-11-23| archive-url= https://web.archive.org/web/20081009193337/http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/index.html| archive-date= 9 October 2008 | url-status= live}}

Cry toxins have specific activities against insect species of the orders Lepidoptera (moths and butterflies), Diptera (flies and mosquitoes), Coleoptera (beetles) and Hymenoptera (wasps, bees, ants and sawflies), as well as against nematodes.{{cite journal | vauthors = Schnepf E, Crickmore N, Van Rie J, Lereclus D, Baum J, Feitelson J, Zeigler DR, Dean DH | title = Bacillus thuringiensis and its pesticidal crystal proteins | journal = Microbiology and Molecular Biology Reviews | volume = 62 | issue = 3 | pages = 775–806 | date = September 1998 | pmid = 9729609 | pmc = 98934 | doi = 10.1128/MMBR.62.3.775-806.1998 }}{{cite journal | vauthors = Wei JZ, Hale K, Carta L, Platzer E, Wong C, Fang SC, Aroian RV | title = Bacillus thuringiensis crystal proteins that target nematodes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 5 | pages = 2760–5 | date = March 2003 | pmid = 12598644 | pmc = 151414 | doi = 10.1073/pnas.0538072100 | bibcode = 2003PNAS..100.2760W | doi-access = free }} A specific example of B. thuringiensis use against beetles is the fight against Colorado Potato Beetles in potato crops. Thus, B. thuringiensis serves as an important reservoir of Cry toxins for production of biological insecticides and insect-resistant genetically modified crops. When insects ingest toxin crystals, their alkaline digestive tracts denature the insoluble crystals, making them soluble and thus amenable to being cut with proteases found in the insect gut, which liberate the toxin from the crystal. The Cry toxin is then inserted into the insect gut cell membrane, paralyzing the digestive tract and forming a pore.{{cite web | vauthors = Cranshaw WS | work = Colorado State University Extension Office. | date = 26 March 2013 | url = http://www.ext.colostate.edu/pubs/insect/05556.html | title = Bacillus thuringiensis Fact Sheet | access-date = 15 January 2013 | archive-date = 6 September 2015 | archive-url = https://web.archive.org/web/20150906000033/http://www.ext.colostate.edu/pubs/insect/05556.html | url-status = dead }} The insect stops eating and starves to death; live Bt bacteria may also colonize the insect, which can contribute to death.{{cite web|vauthors=Babu M, Geetha M|url=http://www.mrc-lmb.cam.ac.uk/genomes/madanm/articles/dnashuff.htm|title=DNA shuffling of Cry proteins|website=Mrc-lmb.cam.ac.uk|access-date=2008-11-23|archive-date=2010-02-12|archive-url=https://web.archive.org/web/20100212131030/http://www.mrc-lmb.cam.ac.uk/genomes/madanm/articles/dnashuff.htm|url-status=dead}} Death occurs within a few hours or weeks.{{Cite web|title=Bacillus thuringiensis (Bt) General Fact Sheet|url=http://npic.orst.edu/factsheets/btgen.html|access-date=2021-01-04|website=npic.orst.edu}} The midgut bacteria of susceptible larvae may be required for B. thuringiensis insecticidal activity.{{cite journal | vauthors = Broderick NA, Raffa KF, Handelsman J | title = Midgut bacteria required for Bacillus thuringiensis insecticidal activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 41 | pages = 15196–9 | date = October 2006 | pmid = 17005725 | pmc = 1622799 | doi = 10.1073/pnas.0604865103 | bibcode = 2006PNAS..10315196B | jstor = 30051525 | doi-access = free }}

A B. thuringiensis small RNA called BtsR1 can silence the Cry5Ba toxin expression when outside the host by binding to the RBS site of the Cry5Ba toxin transcript to avoid nematode behavioral defenses. The silencing results in an increase of the bacteria ingestion by C. elegans. The expression of BtsR1 is then reduced after ingestion, resulting in Cry5Ba toxin production and host death.{{cite journal | vauthors = Peng D, Luo X, Zhang N, Guo S, Zheng J, Chen L, Sun M | title = Small RNA-mediated Cry toxin silencing allows Bacillus thuringiensis to evade Caenorhabditis elegans avoidance behavioral defenses | journal = Nucleic Acids Research | volume = 46 | issue = 1 | pages = 159–173 | date = January 2018 | pmid = 29069426 | pmc = 5758910 | doi = 10.1093/nar/gkx959 }}

In 1996 another class of insecticidal proteins in Bt was discovered: the vegetative insecticidal proteins (Vip; {{InterPro|IPR022180}}).{{cite journal | vauthors = Palma L, Hernández-Rodríguez CS, Maeztu M, Hernández-Martínez P, Ruiz de Escudero I, Escriche B, Muñoz D, Van Rie J, Ferré J, Caballero P | title = Vip3C, a novel class of vegetative insecticidal proteins from Bacillus thuringiensis | journal = Applied and Environmental Microbiology | volume = 78 | issue = 19 | pages = 7163–5 | date = October 2012 | pmid = 22865065 | pmc = 3457495 | doi = 10.1128/AEM.01360-12 | bibcode = 2012ApEnM..78.7163P }}{{cite journal | vauthors = Estruch JJ, Warren GW, Mullins MA, Nye GJ, Craig JA, Koziel MG | title = Vip3A, a novel Bacillus thuringiensis vegetative insecticidal protein with a wide spectrum of activities against lepidopteran insects | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 11 | pages = 5389–94 | date = May 1996 | pmid = 8643585 | pmc = 39256 | doi = 10.1073/pnas.93.11.5389 | bibcode = 1996PNAS...93.5389E | doi-access = free }} Vip proteins do not share sequence homology with Cry proteins, in general do not compete for the same receptors, and some kill different insects than do Cry proteins.

In 2000, a novel subgroup of Cry protein, designated parasporin, was discovered from non-insecticidal B. thuringiensis isolates.{{cite journal | vauthors = Mizuki E, Park YS, Saitoh H, Yamashita S, Akao T, Higuchi K, Ohba M | title = Parasporin, a human leukemic cell-recognizing parasporal protein of Bacillus thuringiensis | journal = Clinical and Diagnostic Laboratory Immunology | volume = 7 | issue = 4 | pages = 625–34 | date = July 2000 | pmid = 10882663 | pmc = 95925 | doi = 10.1128/CDLI.7.4.625-634.2000 }} The proteins of parasporin group are defined as B. thuringiensis and related bacterial parasporal proteins that are not hemolytic, but capable of preferentially killing cancer cells.{{cite journal | vauthors = Ohba M, Mizuki E, Uemori A | title = Parasporin, a new anticancer protein group from Bacillus thuringiensis | journal = Anticancer Research | volume = 29 | issue = 1 | pages = 427–33 | date = January 2009 | pmid = 19331182 | url = http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=19331182 }} As of January 2013, parasporins comprise six subfamilies: PS1 to PS6.{{cite web | title = List of Parasporins | url = http://parasporin.fitc.pref.fukuoka.jp/list.html | work = Official Website of the Committee of Parasporin Classification and Nomenclature | access-date = 4 January 2013}}

Spores and crystalline insecticidal proteins produced by B. thuringiensis have been used to control insect pests since the 1920s and are often applied as liquid sprays and donut pellets.{{cite journal | vauthors = Lemaux PG | title = Genetically Engineered Plants and Foods: A Scientist's Analysis of the Issues (Part I) | journal = Annual Review of Plant Biology | volume = 59 | pages = 771–812 | year = 2008 | pmid = 18284373 | doi = 10.1146/annurev.arplant.58.032806.103840 }} They are now used as specific insecticides under trade names such as DiPel, Thuricide, and Mosquito Dunks.{{Cite web |date=2024-08-09 |title=This Mosquito Hack ACTUALLY Works! |url=https://styleblueprint.com/everyday/mosquito-hack/ |access-date=2025-05-23 |website=styleblueprint.com |language=en-US}}{{Cite web |last=Skwarecki |first=Beth |date=2024-05-02 |title=The Best Way to Keep Mosquitoes From Breeding in Your Yard |url=https://lifehacker.com/how-to-keep-mosquitoes-from-breeding-in-your-yard-1850607465 |access-date=2025-05-23 |website=Lifehacker |language=en}} Because of their specificity, these pesticides are regarded as environmentally friendly, with little or no effect on humans, wildlife, pollinators, and most other beneficial insects, and are used in organic farming; however, the manuals for these products do contain many environmental and human health warnings,{{Cite web |url= http://www.cdms.net/ldat/ld4KK005.pdf |archive-url= https://web.archive.org/web/20130908063221/http://www.cdms.net/ldat/ld4KK005.pdf |url-status=dead|title=DiPelProDf data sheet | publisher = Valent U.S.A Corporation | date = 2005 |archive-date=September 8, 2013}}{{Cite web |url= http://www.cdms.net/ldat/ld4KK007.pdf |archive-url=https://web.archive.org/web/20140313091246/http://www.cdms.net/ldat/ld4KK007.pdf|url-status=dead|title=DiPelProDf data sheet | publisher = Valent U.S.A Corporation | date = 2009 |archive-date=March 13, 2014}} and a 2012 European regulatory peer review of five approved strains found, while data exist to support some claims of low toxicity to humans and the environment, the data are insufficient to justify many of these claims.{{Cite journal|title=Conclusion on the peer review of the pesticide risk assessment of the active substance Bacillus thuringiensis subsp. kurstaki (strains ABTS 351, PB 54, SA 11, SA 12, EG 2348)|date=August 8, 2012|journal=EFSA Journal|volume=10|issue=2|pages=2540|doi=10.2903/j.efsa.2012.2540|doi-access=free}}

New strains of Bt are developed and introduced over time{{cite book | vauthors = Rubin AL | chapter = Microbial Pest Control Agents: Use Patterns, Registration Requirements, and Mammalian Toxicity | chapter-url = https://books.google.com/books?id=sUrLT9z9i3IC&pg=PA442 | veditors = Krieger R |title= Hayes' Handbook of Pesticide Toxicology | volume = 1 |publisher=Academic Press, imprint of Elsevier |year=2010 |pages=442–443|isbn= 978-0-08-092201-0 }} as insects develop resistance to Bt,{{cite journal| vauthors = Huang F, Buschman LL, Higgins RA |title=Larval feeding behavior of Dipel-resistant and susceptible Ostrinia nubilalis on diet containing Bacillus thuringiensis (Dipel EStm) |journal=Entomologia Experimentalis et Applicata|volume=98|issue=2|year=2001|pages= 141–148 |issn=0013-8703|doi=10.1046/j.1570-7458.2001.00768.x|s2cid=86218577 }} or the desire occurs to force mutations to modify organism characteristics{{cite patent | country = US | number = 4910016 |url=https://www.google.com/patents/US4910016 |title=Novel Bacillus thuringiensis isolate | inventor = Gaertner FH, Soares GC, Payne J | assign1 = Mycogen Corp | gdate = 20 March 1990 | postscript = . }}{{clarify|reason=What does this mean?|date=November 2020}}, or to use homologous recombinant genetic engineering to improve crystal size and increase pesticidal activity,{{cite patent |url=https://www.google.com/patents/US6303382 |title=Formation of and methods for the production of large bacillus thuringiensis crystals with increased pesticidal activity | assign1 = Valent BioSciences LLC | inventor = Adams LF, Thomas MD, Sloma AP, Widner WR | country = US | number = 6303382 | gdate = 16 October 2001 | postscript = . }} or broaden the host range of Bt and obtain more effective formulations.{{cite patent |status = patent|url= https://www.google.com/patents/US5955367 |title=Production of bacillus thuringiensis integrants |number=5955367 |country =US |pridate = 1989-12-18 |pubdate = 1999-09-21| inventor = Adams LF }} Each new strain is given a unique number and registered with the U.S. EPA{{cite web|url=http://www.epa.gov/fedrgstr/EPA-PEST/2007/October/Day-26/p20828.htm|title=Pesticides; Data Requirements for Biochemical and Microbial Pesticides|publisher=U.S. Environmental Protection Agency|access-date=2022-04-09}} and allowances may be given for genetic modification depending on "its parental strains, the proposed pesticide use pattern, and the manner and extent to which the organism has been genetically modified".{{Cite web|url=https://www.law.cornell.edu/cfr/text/40/158.2100|title=40 CFR § 158.2100 - Microbial pesticides definition and applicability.|website=Law.cornell.edu|access-date=9 April 2022}} Formulations of Bt that are approved for organic farming in the US are listed at the website of the Organic Materials Review Institute (OMRI){{cite web |url= https://www.omri.org/ubersearch/results/bacillus%20thuringiensis?type[]=materials_article&type[]=opd_generic_listing&type[]=livestock&type[]=opd_listed_product&type[]=opd_prohibited_product&type[]=opd_removed_product |title= Search: bacillus, thuringiensis |publisher=OMRI }} and several university extension websites offer advice on how to use Bt spore or protein preparations in organic farming.{{cite book | veditors = Caldwell B, Sideman E, Seaman A, Shelton A, Smart C |year=2013 |chapter=Material Fact Sheet: Bacillus thuringiensis (Bt) |chapter-url=http://web.pppmb.cals.cornell.edu/resourceguide/pdf/resource-guide-for-organic-insect-and-disease-management.pdf#116 |archive-url=https://ghostarchive.org/archive/20221009/http://web.pppmb.cals.cornell.edu/resourceguide/pdf/resource-guide-for-organic-insect-and-disease-management.pdf#116 |archive-date=2022-10-09 |url-status=live |pages=109–12 |title=Resource Guide for Organic Insect and Disease Management |edition=2nd |url=http://web.pppmb.cals.cornell.edu/resourceguide/ |isbn= 978-0-9676507-8-4}}

The Belgian company Plant Genetic Systems (now part of Bayer CropScience) was the first company (in 1985) to develop genetically modified crops (tobacco) with insect tolerance by expressing cry genes from B. thuringiensis; the resulting crops contain delta endotoxin.{{cite journal | vauthors = Höfte H, de Greve H, Seurinck J, Jansens S, Mahillon J, Ampe C, Vandekerckhove J, Vanderbruggen H, van Montagu M, Zabeau M | title = Structural and functional analysis of a cloned delta endotoxin of Bacillus thuringiensis berliner 1715 | journal = European Journal of Biochemistry | volume = 161 | issue = 2 | pages = 273–80 | date = December 1986 | pmid = 3023091 | doi = 10.1111/j.1432-1033.1986.tb10443.x | display-authors = 6 | doi-access = free }}{{cite journal |doi=10.1038/328033a0 |title=Transgenic plants protected from insect attack |year=1987 | vauthors = Vaeck M, Reynaerts A, Höfte H, Jansens S, de Beuckeleer M, Dean C, Zabeau M, Van Montagu M, Leemans J | display-authors = 6 |journal=Nature |volume=328 |issue=6125 |pages=33–7 |bibcode=1987Natur.328...33V|s2cid=4310501 }} The Bt tobacco was never commercialized; tobacco plants are used to test genetic modifications since they are easy to manipulate genetically and are not part of the food supply.{{cite web | author = Staff | work = GMO Compass | date = 29 July 2010 | url = http://www.gmo-compass.org/eng/database/plants/304.tobacco.html | title = "Tobacco" entry in GMO Compass database | archive-url = https://web.archive.org/web/20131002090217/http://www.gmo-compass.org/eng/database/plants/304.tobacco.html | archive-date = 2 October 2013 }}{{cite journal | vauthors = Key S, Ma JK, Drake PM | title = Genetically modified plants and human health | journal = Journal of the Royal Society of Medicine | volume = 101 | issue = 6 | pages = 290–8 | date = June 2008 | pmid = 18515776 | pmc = 2408621 | doi = 10.1258/jrsm.2008.070372 }}

Image:Bt plants.png leaves (bottom dish) protect it from extensive damage caused to unprotected peanut leaves by lesser cornstalk borer larvae (top dish).{{cite web | vauthors = Suszkiwn J |url= http://ars.usda.gov/is/ar/archive/nov99/pest1199.htm |title=Tifton, Georgia: A Peanut Pest Showdown |access-date=2008-11-23 |work= Agricultural Research magazine|date=November 1999| archive-url= https://web.archive.org/web/20081012182444/http://www.ars.usda.gov/is/AR/archive/nov99/pest1199.htm| archive-date= 12 October 2008 | url-status= live}}]]

In 1995, {{visible anchor|Bt potato|text=potato plants producing CRY 3A Bt toxin}} were approved safe by the Environmental Protection Agency, making it the first human-modified pesticide-producing crop to be approved in the US,{{cite news|url = https://news.google.com/newspapers?id=A0YyAAAAIBAJ&pg=4631,1776980&dq=bacillus+thuringiensis+potato+1996+approved&hl= |title = Genetically Altered Potato Ok'd For Crops |work = Lawrence Journal-World |date = 6 May 1995|agency = AP|via = Google News}}{{cite web |url=http://www.cera-gmc.org/files/cera/GmCropDatabase/docs/decdocs/02-269-004.pdf |title=Safety Assessment of NewLeaf ®Y Potatoes Protected Against Colorado Potato Beetle and Infection by Potato Virus Y Causing Rugose Mosaic |website=www.cera-gmc.org |access-date=31 August 2022 |archive-url=https://web.archive.org/web/20150927213821/http://www.cera-gmc.org/files/cera/GmCropDatabase/docs/decdocs/02-269-004.pdf |archive-date=27 September 2015 |url-status=dead}} though many plants produce pesticides naturally, including tobacco, coffee plants, cocoa, cotton and black walnut. This was the 'New Leaf' potato, and it was removed from the market in 2001 due to lack of interest.{{cite news|title=The History and Future of GM Potatoes| vauthors = van Eijck P |url=http://www.potatopro.com/newsletters/20100310.htm|newspaper=PotatoPro Newsletter|date=March 10, 2010|access-date=October 5, 2013|archive-url=https://web.archive.org/web/20131012033805/http://www.potatopro.com/newsletters/20100310.htm|archive-date=October 12, 2013|url-status=dead}}

In 1996, {{visible anchor|Bt maize|Bt corn|text=genetically modified maize producing Bt Cry protein}} was approved, which killed the European corn borer and related species; subsequent Bt genes were introduced that killed corn rootworm larvae.{{cite journal | vauthors = Hellmich RL, Hellmich KA | year = 2012 | title = Use and Impact of Bt Maize | url = http://www.nature.com/scitable/knowledge/library/use-and-impact-of-bt-maize-46975413 | journal = Nature Education Knowledge | volume = 3 | issue = 10| page = 4 }}

The Bt genes engineered into crops and approved for release include, singly and stacked: Cry1A.105, CryIAb, CryIF, Cry2Ab, Cry3Bb1, Cry34Ab1, Cry35Ab1, mCry3A, and VIP, and the engineered crops include corn and cotton.{{cite web | vauthors = Bessin R | work = University of Kentucky College of Agriculture | orig-date = May 1996 | date = November 2010 | url = http://www2.ca.uky.edu/entomology/entfacts/ef118.asp | title = Bt-Corn for Corn Borer Control }}{{cite book | vauthors = Castagnola AS, Jurat-Fuentes JL | chapter = Bt Crops: Past and Future. Chapter 15 | title = Bacillus thuringiensis Biotechnology | veditors = Sansinenea E | publisher = Springer | date = March 2012 | isbn = 978-94-007-3020-5 }}{{rp|285ff}}

Corn genetically modified to produce VIP was first approved in the US in 2010.{{cite web | vauthors = Hodgson E, Gassmann A | work = Iowa State Extension, Department of Entomology. | date = May 2010 | url = http://www.extension.iastate.edu/CropNews/2010/0510hodgsongassman.htm | title = New Corn Trait Deregulated in U.S. }}

In India, by 2014, more than seven million cotton farmers, occupying twenty-six million acres, had adopted {{visible anchor|Bt cotton}}.{{cite magazine | url = http://www.newyorker.com/magazine/2014/08/25/seeds-of-doubt | title = Seeds of Doubt: An activist's controversial crusade against genetically modified crops. | vauthors = Specter M | magazine = The New Yorker | date = 25 August 2014 }}

Monsanto developed a {{visible anchor|Bt soybean|text=soybean expressing Cry1Ac}} and the glyphosate-resistance gene for the Brazilian market, which completed the Brazilian regulatory process in 2010.{{cite web | author = Staff | work = Monsanto | date = August 2009 | url = http://www.gmo-compass.org/pdf/regulation/soybean/MON87701xMON89788_soybean_application_food_feed.pdf | title = Application for authorization to place on the market MON 87701 × MON 89788 soybean in the European Union, according to Regulation (EC) No 1829/2003 on genetically modified food and feed | archive-url = https://web.archive.org/web/20120905233938/http://www.gmo-compass.org/pdf/regulation/soybean/MON87701xMON89788_soybean_application_food_feed.pdf | archive-date=2012-09-05 }} Linked from the {{cite web | work = GMO Compass | url = http://www.gmo-compass.org/eng/gmo/db/147.docu.html | title = MON87701 x MON89788 | archive-url = https://web.archive.org/web/20131109152621/http://www.gmo-compass.org/eng/gmo/db/147.docu.html | archive-date=2013-11-09 }}{{Cite web|url=http://www.isaaa.org/kc/cropbiotechupdate/article/default.asp?ID=6565|title=Monsanto's Bt Roundup Ready 2 Yield Soybeans Approved for Planting in Brazil| work = Crop Biotech Update | date = 27 August 2010 | publisher = International Service for the Acquisition of Agri-biotech Applications (ISAAA) }}

{{visible anchor|Bt aspen|Bt-transformed aspens}} - specifically Populus hybrids - have been developed. They do suffer lesser leaf damage from insect herbivory. The results have not been entirely positive however: The intended result - better timber yield - was not achieved, with no growth advantage despite that reduction in herbivore damage; one of their major pests still preys upon the transgenic trees; and besides that, their leaf litter decomposes differently due to the transgenic toxins, resulting in alterations to the aquatic insect populations nearby.{{cite journal | vauthors = Stange M, Barrett RD, Hendry AP | title = The importance of genomic variation for biodiversity, ecosystems and people | journal = Nature Reviews. Genetics | volume = 22 | issue = 2 | pages = 89–105 | date = February 2021 | pmid = 33067582 | doi = 10.1038/s41576-020-00288-7 | publisher = Nature Research | s2cid = 223559538 }}

Image:Btcornafrica.jpg Bt corn]]

The use of Bt toxins as plant-incorporated protectants prompted the need for extensive evaluation of their safety for use in foods and potential unintended impacts on the environment.{{Cite web|url=https://gmoscience.org/2015/08/10/is-bt-toxin-safe/|title=Are all forms of Bt toxin safe?|website=Gmoscience.org|access-date=9 April 2022}}

Concerns over the safety of consumption of genetically modified plant materials that contain Cry proteins have been addressed in extensive dietary risk assessment studies. As a toxic mechanism, cry proteins bind to specific receptors on the membranes of mid-gut (epithelial) cells of the targeted pests, resulting in their rupture. While the target pests are exposed to the toxins primarily through leaf and stalk material, Cry proteins are also expressed in other parts of the plant, including trace amounts in maize kernels which are ultimately consumed by both humans and animals.{{cite journal | vauthors = Fearing PL, Brown D, Vlachos D, Meghji M, Privalle L | title = Quantitative analysis of CryIA (b) expression in Bt maize plants, tissues, and silage and stability of expression over successive generations. | journal = Molecular Breeding | date = June 1997 | volume = 3 | issue = 3 | pages = 169–176 | doi = 10.1023/A:1009611613475 | s2cid = 34209572 }} However, other organisms (including humans, other animals and non-targeted insects) that lack the appropriate receptors in their gut cannot be affected by the cry protein, and therefore are not affected by Bt.

Animal models have been used to assess human health risk from consumption of products containing Cry proteins. The United States Environmental Protection Agency recognizes mouse acute oral feeding studies where doses as high as 5,000 mg/kg body weight resulted in no observed adverse effects.{{cite web|publisher=US EPA|date=2001|url=http://www3.epa.gov/pesticides/chem_search/reg_actions/pip/bt_brad2/2-id_health.pdf |archive-url=https://web.archive.org/web/20151211051629/http://www3.epa.gov/pesticides/chem_search/reg_actions/pip/bt_brad2/2-id_health.pdf |archive-date=2015-12-11 |url-status=live|title=Bt Plant-Incorporated Protectants October 15, 2001 Biopesticides Registration Action Document|access-date=2022-04-09}} Research on other known toxic proteins suggests that {{clarify|text=toxicity occurs at much lower doses|reason=This statement is likely the opposite of what was intended.|date=November 2020}}, further suggesting that Bt toxins are not toxic to mammals.{{cite journal | vauthors = Sjoblad RD, McClintock JT, Engler R | title = Toxicological considerations for protein components of biological pesticide products | journal = Regulatory Toxicology and Pharmacology | volume = 15 | issue = 1 | pages = 3–9 | date = February 1992 | pmid = 1553409 | doi = 10.1016/0273-2300(92)90078-n | url = https://zenodo.org/record/1258447 }} The results of toxicology studies are further strengthened by the lack of observed toxicity from decades of use of B. thuringiensis and its crystalline proteins as an insecticidal spray.{{cite journal | vauthors = Koch MS, Ward JM, Levine SL, Baum JA, Vicini JL, Hammond BG | title = The food and environmental safety of Bt crops | journal = Frontiers in Plant Science | volume = 6 | pages = 283 | date = April 2015 | pmid = 25972882 | pmc = 4413729 | doi = 10.3389/fpls.2015.00283 | doi-access = free }}

Introduction of a new protein raised concerns regarding the potential for allergic responses in sensitive individuals. Bioinformatic analysis of known allergens has indicated there is no concern of allergic reactions as a result of consumption of Bt toxins.{{cite journal | vauthors = Randhawa GJ, Singh M, Grover M | title = Bioinformatic analysis for allergenicity assessment of Bacillus thuringiensis Cry proteins expressed in insect-resistant food crops | journal = Food and Chemical Toxicology | volume = 49 | issue = 2 | pages = 356–62 | date = February 2011 | pmid = 21078358 | doi = 10.1016/j.fct.2010.11.008 }} Additionally, skin prick testing using purified Bt protein resulted in no detectable production of toxin-specific IgE antibodies, even in atopic patients.{{cite journal | vauthors = Batista R, Nunes B, Carmo M, Cardoso C, José HS, de Almeida AB, Manique A, Bento L, Ricardo CP, Oliveira MM | title = Lack of detectable allergenicity of transgenic maize and soya samples | journal = The Journal of Allergy and Clinical Immunology | volume = 116 | issue = 2 | pages = 403–10 | date = August 2005 | pmid = 16083797 | doi = 10.1016/j.jaci.2005.04.014 | url = http://repositorio.insa.pt/bitstream/10400.18/114/1/Lack%20of%20detectable%20allergenicity.pdf | hdl = 10400.18/114 }}

Studies have been conducted to evaluate the fate of Bt toxins that are ingested in foods. Bt toxin proteins have been shown to digest within minutes of exposure to simulated gastric fluids.{{cite journal | vauthors = Betz FS, Hammond BG, Fuchs RL | title = Safety and advantages of Bacillus thuringiensis-protected plants to control insect pests | journal = Regulatory Toxicology and Pharmacology | volume = 32 | issue = 2 | pages = 156–73 | date = October 2000 | pmid = 11067772 | doi = 10.1006/rtph.2000.1426 }} The instability of the proteins in digestive fluids is an additional indication that Cry proteins are unlikely to be allergenic, since most known food allergens resist degradation and are ultimately absorbed in the small intestine.{{cite journal | vauthors = Astwood JD, Leach JN, Fuchs RL | title = Stability of food allergens to digestion in vitro | journal = Nature Biotechnology | volume = 14 | issue = 10 | pages = 1269–73 | date = October 1996 | pmid = 9631091 | doi = 10.1038/nbt1096-1269 | s2cid = 22780150 }}

Concerns over possible environmental impact from accumulation of Bt toxins from plant tissues, pollen dispersal, and direct secretion from roots have been investigated. Bt toxins may persist in soil for over 200 days, with half-lives between 1.6 and 22 days. Much of the toxin is initially degraded rapidly by microorganisms in the environment, while some is adsorbed by organic matter and persists longer.{{cite book | vauthors = Helassa N, Quiquampoix H, Staunton S | veditors = Xu J, Sparks D | title=Molecular Environmental Soil Science|date=2013|publisher=Springer Netherlands|isbn=978-94-007-4177-5|pages=49–77|chapter=Structure, Biological Activity and Environmental Fate of Insecticidal Bt (Bacillus thuringiensis) Cry Proteins of Bacterial and Genetically Modified Plant Origin| doi = 10.1007/978-94-007-4177-5_3 }} Some studies, in contrast, claim that the toxins do not persist in the soil.{{cite journal | vauthors = Dubelman S, Ayden BR, Bader BM, Brown CR, Jiang, Vlachos D | year = 2005 | title = Cry1Ab Protein Does Not Persist in Soil After 3 Years of Sustained Bt Corn Use | journal = Environ. Entomol. | volume = 34 | issue = 4| pages = 915–921 | doi=10.1603/0046-225x-34.4.915| doi-access = free }}{{cite journal | vauthors = Head G, Surber JB, Watson JA, Martin JW, Duan JJ | year = 2002 | title = No Detection of Cry1Ac Protein in Soil After Multiple Years of Transgenic Bt Cotton (Bollgard) Use | journal = Environ. Entomol. | volume = 31 | issue = 1| pages = 30–36 | doi=10.1603/0046-225x-31.1.30| doi-access = free }} Bt toxins are less likely to accumulate in bodies of water, but pollen shed or soil runoff may deposit them in an aquatic ecosystem. Fish species are not susceptible to Bt toxins if exposed.{{cite journal | vauthors = Clark BW, Phillips TA, Coats JR | title = Environmental fate and effects of Bacillus thuringiensis (Bt) proteins from transgenic crops: a review | journal = Journal of Agricultural and Food Chemistry | volume = 53 | issue = 12 | pages = 4643–53 | date = June 2005 | pmid = 15941295 | doi = 10.1021/jf040442k | hdl = 10161/6458 | url = http://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/6458/Clark%20et%20al.%202005%20Bt%20Review.pdf?sequence=1 }}

The toxic nature of Bt proteins has an adverse impact on many major crop pests, but some ecological risk assessments has been conducted to ensure safety of beneficial non-target organisms that may come into contact with the toxins. Toxicity for the monarch butterfly, has been shown to not reach dangerous levels.{{cite journal | vauthors = Sears MK, Hellmich RL, Stanley-Horn DE, Oberhauser KS, Pleasants JM, Mattila HR, Siegfried BD, Dively GP | title = Impact of Bt corn pollen on monarch butterfly populations: a risk assessment | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 21 | pages = 11937–42 | date = October 2001 | pmid = 11559842 | pmc = 59819 | doi = 10.1073/pnas.211329998 | bibcode = 2001PNAS...9811937S | doi-access = free }} Most soil-dwelling organisms, potentially exposed to Bt toxins through root exudates, are probably not impacted by the growth of Bt crops.{{cite journal | vauthors = Saxena D, Stotzky G | year = 2000 | title = Bacillus thuringiensis (Bt) toxin released from root exudates and biomass of Bt corn has no apparent effect on earthworms, nematodes, protozoa, bacteria, and fungi in soil | url = http://www.ask-force.org/web/Bt/Saxena-Stotzky-2001.pdf | journal = Soil Biology & Biochemistry | volume = 33 | issue = 9| pages = 1225–1230 | doi=10.1016/s0038-0717(01)00027-x}}

Multiple insects have developed a resistance to B. thuringiensis. In November 2009, Monsanto scientists found the pink bollworm had become resistant to the first-generation Bt cotton in parts of Gujarat, India - that generation expresses one Bt gene, Cry1Ac. This was the first instance of Bt resistance confirmed by Monsanto anywhere in the world.{{cite web|url=http://www.monsanto.com/newsviews/Pages/india-pink-bollworm.aspx |title=Cotton in India |publisher=Monsanto.com |date=2008-11-03 |access-date=2013-07-09}}{{cite journal | vauthors = Bagla P | title = India. Hardy cotton-munching pests are latest blow to GM crops | journal = Science | volume = 327 | issue = 5972 | pages = 1439 | date = March 2010 | pmid = 20299559 | doi = 10.1126/science.327.5972.1439 | bibcode = 2010Sci...327.1439B | doi-access = free }} Monsanto responded by introducing a second-generation cotton with multiple Bt proteins, which was rapidly adopted. Bollworm resistance to first-generation Bt cotton was also identified in Australia, China, Spain, and the United States.{{cite journal | vauthors = Tabashnik BE, Gassmann AJ, Crowder DW, Carriére Y | title = Insect resistance to Bt crops: evidence versus theory | journal = Nature Biotechnology | volume = 26 | issue = 2 | pages = 199–202 | date = February 2008 | pmid = 18259177 | doi = 10.1038/nbt1382 | s2cid = 205273664 }} Additionally, resistance to Bt was documented in field population of diamondback moth in Hawaii, the continental US, and Asia.{{cite journal | vauthors = Tabshnik BE |title=Evolution of Resistance to Bacillus Thuringiensis |journal=Annual Review of Entomology |date=January 1994 |volume= 39 |pages=47–79 |doi= 10.1146/annurev.en.39.010194.000403}} Studies in the cabbage looper have suggested that a mutation in the membrane transporter ABCC2 can confer resistance to Bt Cry1Ac.{{cite journal | vauthors = Baxter SW, Badenes-Pérez FR, Morrison A, Vogel H, Crickmore N, Kain W, Wang P, Heckel DG, Jiggins CD | title = Parallel evolution of Bacillus thuringiensis toxin resistance in lepidoptera | journal = Genetics | volume = 189 | issue = 2 | pages = 675–9 | date = October 2011 | pmid = 21840855 | pmc = 3189815 | doi = 10.1534/genetics.111.130971 }}

Several studies have documented surges in "sucking pests" (which are not affected by Bt toxins) within a few years of adoption of Bt cotton. In China, the main problem has been with mirids,{{cite journal | vauthors = Lu Y, Wu K, Jiang Y, Xia B, Li P, Feng H, Wyckhuys KA, Guo Y | title = Mirid bug outbreaks in multiple crops correlated with wide-scale adoption of Bt cotton in China | journal = Science | volume = 328 | issue = 5982 | pages = 1151–4 | date = May 2010 | pmid = 20466880 | doi = 10.1126/science.1187881 | bibcode = 2010Sci...328.1151L | s2cid = 2093962 | doi-access = free }}{{cite conference | vauthors = Just DR, Wang S, Pinstrup-Andersen P |year=2006 |title=Tarnishing Silver Bullets: Bt Technology Adoption, Bounded Rationality and the Outbreak of Secondary Pest Infestations in China |conference=American Agricultural Economics Association Annual Meeting |location=Long Beach, CA |url=http://purl.umn.edu/21230}}

• {{cite news | vauthors = Lang S |date=July 25, 2006 |title=Seven-year glitch: Cornell warns that Chinese GM cotton farmers are losing money due to 'secondary' pests |newspaper=Cornell Chronicle |url=http://www.news.cornell.edu/stories/July06/Bt.cotton.China.ssl.html |archive-url=https://web.archive.org/web/20060811215559/http://www.news.cornell.edu/stories/July06/Bt.cotton.China.ssl.html |archive-date=2006-08-11}} which have in some cases "completely eroded all benefits from Bt cotton cultivation".{{cite journal |doi=10.1504/IJBT.2008.018348 |title=Bt-cotton and secondary pests |year=2008 | vauthors = Wang S, Just DR, Pinstrup-Andersen P |journal=International Journal of Biotechnology |volume=10 |issue=2/3 |pages=113–21}} The increase in sucking pests depended on local temperature and rainfall conditions and increased in half the villages studied. The increase in insecticide use for the control of these secondary insects was far smaller than the reduction in total insecticide use due to Bt cotton adoption.{{cite journal | vauthors = Wang Z, Lin H, Huang J, Hu R, Rozelle S, Pray C |doi=10.1016/S1671-2927(09)60012-2 |title=Bt Cotton in China: Are Secondary Insect Infestations Offsetting the Benefits in Farmer Fields? |year=2009 |journal=Agricultural Sciences in China |volume=8 |pages=83–90}} Another study in five provinces in China found the reduction in pesticide use in Bt cotton cultivars is significantly lower than that reported in research elsewhere, consistent with the hypothesis suggested by recent studies that more pesticide sprayings are needed over time to control emerging secondary pests, such as aphids, spider mites, and lygus bugs.{{cite journal | vauthors = Zhao JH, Ho P, Azadi H | title = Benefits of Bt cotton counterbalanced by secondary pests? Perceptions of ecological change in China | journal = Environmental Monitoring and Assessment | volume = 173 | issue = 1–4 | pages = 985–994 | date = February 2011 | pmid = 20437270 | doi = 10.1007/s10661-010-1439-y | s2cid = 1583208 }}; Erratum published 2012 Aug 5: {{cite journal | vauthors = Zhao JH, Ho P, Azadi H |doi=10.1007/s10661-012-2699-5 |title=Erratum to: Benefits of Bt cotton counterbalanced by secondary pests? Perceptions of ecological change in China |year=2012 |journal=Environmental Monitoring and Assessment |volume=184 |issue=11 |page=7079 |doi-access=free }}

Similar problems have been reported in India, with both mealy bugs{{cite web | vauthors = Goswami B | work = InfoChange | url = http://infochangeindia.org/200709026463/Other/Features/Making-a-meal-of-Bt-cotton.html | archive-url = https://web.archive.org/web/20080616053151/http://infochangeindia.org/200709026463/Other/Features/Making-a-meal-of-Bt-cotton.html | archive-date = 16 June 2008 | title = Making a meal of Bt cotton | access-date = 6 April 2009 }}{{cite news|url=http://www.gmwatch.org/en/news/archive/2007/7640-bug-makes-meal-of-punjab-cotton-whither-bt-magic-492007 |access-date=14 March 2018 |title=Bug makes meal of Punjab cotton, whither Bt magic? |date=4 September 2007 |newspaper=The Economic Times}} and aphids{{cite journal |doi=10.1016/j.worlddev.2010.09.008 |title=Field versus Farm in Warangal: Bt Cotton, Higher Yields, and Larger Questions |year=2011 | vauthors = Stone GD |journal=World Development |volume=39 |issue=3 |pages=387–98}} although a survey of small Indian farms between 2002 and 2008 concluded Bt cotton adoption has led to higher yields and lower pesticide use, decreasing over time.{{cite journal |doi=10.1016/j.agsy.2011.11.005 |title=Bt cotton and sustainability of pesticide reductions in India |year=2012 | vauthors = Krishna VV, Qaim M |journal=Agricultural Systems |volume=107 |pages=47–55}}

The controversies surrounding Bt use are among the many genetically modified food controversies more widely.{{Cite web|url=https://www.pbs.org/wgbh/harvest/viewpoints/|title= Harvest of fear: viewpoints | work = Frontline/NOVA | publisher = Public Broadcasting Service | date = 2001 |access-date=9 April 2022}}

The most publicised problem associated with Bt crops is the claim that pollen from Bt maize could kill the monarch butterfly.{{cite journal | vauthors = Losey JE, Rayor LS, Carter ME | title = Transgenic pollen harms monarch larvae | journal = Nature | volume = 399 | issue = 6733 | pages = 214 | date = May 1999 | pmid = 10353241 | doi = 10.1038/20338 | bibcode = 1999Natur.399..214L | s2cid = 4424836 | doi-access = free }} The paper produced a public uproar and demonstrations against Bt maize; however by 2001 several follow-up studies coordinated by the USDA had asserted that "the most common types of Bt maize pollen are not toxic to monarch larvae in concentrations the insects would encounter in the fields."{{cite journal | vauthors = Waltz E | journal = Nature News | date = 2 September 2009 | doi = 10.1038/461027a | title = GM crops: Battlefield | volume = 461 | issue = 7260 | pages = 27–32 | pmid = 19727179 | s2cid = 205048726 }}{{cite journal | vauthors = Mendelsohn M, Kough J, Vaituzis Z, Matthews K | title = Are Bt crops safe? | journal = Nature Biotechnology | volume = 21 | issue = 9 | pages = 1003–9 | date = September 2003 | pmid = 12949561 | doi = 10.1038/nbt0903-1003 | s2cid = 16392889 | url = https://zenodo.org/record/1233343 }}{{cite journal | vauthors = Hellmich RL, Siegfried BD, Sears MK, Stanley-Horn DE, Daniels MJ, Mattila HR, Spencer T, Bidne KG, Lewis LC | title = Monarch larvae sensitivity to Bacillus thuringiensis- purified proteins and pollen | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 21 | pages = 11925–30 | date = October 2001 | pmid = 11559841 | pmc = 59744 | doi = 10.1073/pnas.211297698 | bibcode = 2001PNAS...9811925H | display-authors = 6 | jstor = 3056825 | doi-access = free }}{{cite web |url=http://www.ars.usda.gov/is/br/btcorn/ |title=Bt Corn and Monarch Butterflies |date=2004-03-29 |work=USDA Agricultural Research Service |access-date=2008-11-23| archive-url= https://web.archive.org/web/20081106062846/http://www.ars.usda.gov/is/br/btcorn/| archive-date= 6 November 2008 | url-status= live}} Similarly, B. thuringiensis has been widely used for controlling Spodoptera littoralis larvae growth due to their detrimental pest activities in Africa and Southern Europe. However, S. littoralis showed resistance to many strains of B. thuriginesis and were only effectively controlled by a few strains.{{cite journal|vauthors=Salama HS, Foda MS, Sharaby A|title=A proposed new biological standard for bioassay of bacterial insecticides vs. Spodoptera spp.|journal=Tropical Pest Management|date=1989|volume=35|issue=3|pages=326–330|url=https://www.cabi.org/isc/abstract/19901181560|doi=10.1080/09670878909371391|access-date=2017-11-12|archive-date=2018-09-29|archive-url=https://web.archive.org/web/20180929194738/https://www.cabi.org/isc/abstract/19901181560|url-status=dead|url-access=subscription}}

A study published in Nature in 2001 reported Bt-containing maize genes were found in maize in its center of origin, Oaxaca, Mexico.{{cite journal | vauthors = Quist D, Chapela IH | title = Transgenic DNA introgressed into traditional maize landraces in Oaxaca, Mexico | journal = Nature | volume = 414 | issue = 6863 | pages = 541–3 | date = November 2001 | pmid = 11734853 | doi = 10.1038/35107068 | bibcode = 2001Natur.414..541Q | s2cid = 4403182 }} Another Nature paper published in 2002 claimed that the previous paper's conclusion was the result of an artifact caused by an inverse polymerase chain reaction and that "the evidence available is not sufficient to justify the publication of the original paper."{{cite journal | vauthors = Kaplinsky N, Braun D, Lisch D, Hay A, Hake S, Freeling M | title = Biodiversity (Communications arising): maize transgene results in Mexico are artefacts | journal = Nature | volume = 416 | issue = 6881 | pages = 601–2; discussion 600, 602 | date = April 2002 | pmid = 11935145 | doi = 10.1038/nature739 | bibcode = 2002Natur.416..601K | s2cid = 195690886 }} A significant controversy happened over the paper and Nature{{'}}s unprecedented notice.{{Cite web | url=https://www.pbs.org/now/science/genenature.html | archive-url = https://web.archive.org/web/20030220201414/https://www.pbs.org/now/science/genenature.html | archive-date = 20 February 2003 | title=Seeds of Conflict: NATURE Article Debate | work = NOW with Bill Moyers. Science & Health. | publisher = PBS }}

A subsequent large-scale study in 2005 failed to find any evidence of genetic mixing in Oaxaca.{{cite journal | vauthors = Ortiz-García S, Ezcurra E, Schoel B, Acevedo F, Soberón J, Snow AA | title = Absence of detectable transgenes in local landraces of maize in Oaxaca, Mexico (2003-2004) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 35 | pages = 12338–43 | date = August 2005 | pmid = 16093316 | pmc = 1184035 | doi = 10.1073/pnas.0503356102 | bibcode = 2005PNAS..10212338O | jstor = 3376579 | doi-access = free }} A 2007 study found the "transgenic proteins expressed in maize were found in two (0.96%) of 208 samples from farmers' fields, located in two (8%) of 25 sampled communities." Mexico imports a substantial amount of maize from the U.S., and due to formal and informal seed networks among rural farmers, many potential routes are available for transgenic maize to enter into food and feed webs.{{cite journal |doi=10.1890/1540-9295(2007)5[247:TPIMIT]2.0.CO;2 |year=2007 |volume=5 |pages=247–52 |title=Transgenic proteins in maize in the Soil Conservation area of Federal District, Mexico | vauthors = Serratos-Hernández J, Gómez-Olivares J, Salinas-Arreortua N, Buendía-Rodríguez E, Islas-Gutiérrez F, De-Ita A |journal=Frontiers in Ecology and the Environment |issue=5 |issn=1540-9295}} One study found small-scale (about 1%) introduction of transgenic sequences in sampled fields in Mexico; it did not find evidence for or against this introduced genetic material being inherited by the next generation of plants.{{cite journal | vauthors = Piñeyro-Nelson A, Van Heerwaarden J, Perales HR, Serratos-Hernández JA, Rangel A, Hufford MB, Gepts P, Garay-Arroyo A, Rivera-Bustamante R, Alvarez-Buylla ER | title = Transgenes in Mexican maize: molecular evidence and methodological considerations for GMO detection in landrace populations | journal = Molecular Ecology | volume = 18 | issue = 4 | pages = 750–61 | date = February 2009 | pmid = 19143938 | pmc = 3001031 | doi = 10.1111/j.1365-294X.2008.03993.x | display-authors = 6 }}{{cite journal | vauthors = Dalton R | title = Modified genes spread to local maize | journal = Nature | volume = 456 | issue = 7219 | pages = 149 | date = November 2008 | pmid = 19005518 | doi = 10.1038/456149a | doi-access = free }} That study was immediately criticized, with the reviewer writing, "Genetically, any given plant should be either non-transgenic or transgenic, therefore for leaf tissue of a single transgenic plant, a GMO level close to 100% is expected. In their study, the authors chose to classify leaf samples as transgenic despite GMO levels of about 0.1%. We contend that results such as these are incorrectly interpreted as positive and are more likely to be indicative of contamination in the laboratory."{{cite journal | vauthors = Schoel B, Fagan J | title = Insufficient evidence for the discovery of transgenes in Mexican landraces | journal = Molecular Ecology | volume = 18 | issue = 20 | pages = 4143–4; discussion 4145–50 | date = October 2009 | pmid = 19793201 | doi = 10.1111/j.1365-294X.2009.04368.x | s2cid = 205362226 | doi-access = free }}

As of 2007, a new phenomenon called colony collapse disorder (CCD) began affecting bee hives all over North America. Initial speculation on possible causes included new parasites, pesticide use,{{cite web |url=http://www.ars.usda.gov/News/docs.htm?docid=15572 |title=ARS: Questions and Answers: Colony Collapse Disorder |work=ARS News | publisher = Agricultural Research Service, United States Department of Agriculture |date=2008-05-29 | access-date=2008-11-23| archive-url = https://web.archive.org/web/20081105121119/http://www.ars.usda.gov/News/docs.htm?docid=15572 | archive-date = 5 November 2008 | url-status= dead }} and the use of Bt transgenic crops.{{cite news | vauthors = Latsch G | title = Are GM Crops Killing Bees? |work=Spiegel Online |date=March 22, 2007 |url=http://www.spiegel.de/international/world/collapsing-colonies-are-gm-crops-killing-bees-a-473166.html}} The Mid-Atlantic Apiculture Research and Extension Consortium found no evidence that pollen from Bt crops is adversely affecting bees.{{cite journal |doi=10.1051/apido:2007022 |title=Effects of Bt corn pollen on honey bees: Emphasis on protocol development |year=2007 | vauthors = Rose R, Dively GP, Pettis J |journal=Apidologie |volume=38 |issue=4 |pages=368–77|s2cid=18256663 |url=https://hal.archives-ouvertes.fr/hal-00892271/document }} According to the USDA, "Genetically modified (GM) crops, most commonly Bt corn, have been offered up as the cause of CCD. But there is no correlation between where GM crops are planted and the pattern of CCD incidents. Also, GM crops have been widely planted since the late 1990s, but CCD did not appear until 2006. In addition, CCD has been reported in countries that do not allow GM crops to be planted, such as Switzerland. German researchers have noted in one study a possible correlation between exposure to Bt pollen and compromised immunity to Nosema."{{cite web | publisher = United States Department of Agriculture | url = http://www.ars.usda.gov/is/AR/archive/jul12/colony0712.htm | title = Colony Collapse Disorder: An Incomplete Puzzle | work = Agricultural Research Magazine | date = July 2012 }} The actual cause of CCD was unknown in 2007, and scientists believe it may have multiple exacerbating causes.{{cite news |url=http://news.bbc.co.uk/1/hi/sci/tech/7925397.stm |title='No proof' of bee killer theory | vauthors = McGrath M |date=5 March 2009 |work=BBC News}}

Some isolates of B. thuringiensis produce a class of insecticidal small molecules called beta-exotoxin, the common name for which is thuringiensin.{{cite web|url=http://ofmpub.epa.gov/apex/pesticides/f?p=CHEMICALSEARCH:3:0::NO:1,3,31,7,12,25:P3_XCHEMICAL_ID:4063 |archive-url=https://archive.today/20130409224957/http://ofmpub.epa.gov/apex/pesticides/f?p=CHEMICALSEARCH:3:0::NO:1,3,31,7,12,25:P3_XCHEMICAL_ID:4063 |url-status=dead |archive-date=2013-04-09 | title = Thuringiensin | work = EPA pesticide database |publisher=Ofmpub.epa.gov |date=2010-11-17 |access-date=2013-07-09 }} A consensus document produced by the OECD says: "Beta-exotoxins are known to be toxic to humans and almost all other forms of life and its presence is prohibited in B. thuringiensis microbial products".{{cite web|title=Consensus Document on Safety Information on Transgenic Plants Expressing Bacillus Thuringiensis - Derived Insect Control Proteins | author = Environment Directorate |location=Paris|date=26 July 2007|quotation=OECD Environment, Health and Safety Publications, Series on Harmonisation of Regulatory Oversight in Biotechnology No. 42 |url=https://www.oecd.org/science/biotrack/46815888.pdf |archive-url=https://web.archive.org/web/20160118053047/http://www.oecd.org/science/biotrack/46815888.pdf |archive-date=2016-01-18 |url-status=live|publisher=Organisation for Economic Co-operation and Development (OECD) }} Thuringiensins are nucleoside analogues. They inhibit RNA polymerase activity, a process common to all forms of life, in rats and bacteria alike.{{cite thesis | vauthors = Yin R |title=Structural basis of transcription inhibition by the nucleoside-analog inhibitor thuringiensin |date=2016 |doi=10.7282/T3S75JHW |url=https://rucore.libraries.rutgers.edu/rutgers-lib/50492/ |publisher=Rutgers University - Graduate School - New Brunswick }}

This bacterium is an opportunistic pathogen of animals other than insects, causing necrosis, pulmonary infection, and/or food poisoning. It is unknown how common this is, because these infections are always taken to be B. cereus infections and are rarely tested for the Cry and Cyt proteins that are the only factor distinguishing B. thuringiensis from B. cereus.

Bacillus thuringiensis is no longer the sole source of pesticidal proteins. The Bacterial Pesticidal Protein Resource Center (BPPRC) provides information on the rapidly expanding field of pesticidal proteins for academics, regulators, and research and development personnel.{{cite journal | vauthors = Crickmore N, Berry C, Panneerselvam S, Mishra R, Connor TR, Bonning BC | title = A structure-based nomenclature for Bacillus thuringiensis and other bacteria-derived pesticidal proteins | journal = Journal of Invertebrate Pathology | volume = 186 | pages = 107438 | date = November 2021 | pmid = 32652083 | doi = 10.1016/j.jip.2020.107438 | s2cid = 220488006 | doi-access = free }}{{cite journal | vauthors = Jurat-Fuentes JL, Heckel DG, Ferré J | title = Mechanisms of Resistance to Insecticidal Proteins from Bacillus thuringiensis | journal = Annual Review of Entomology | volume = 66 | issue = 1 | pages = 121–140 | date = January 2021 | pmid = 33417820 | doi = 10.1146/annurev-ento-052620-073348 | s2cid = 231303932 | doi-access = free }}{{cite journal | vauthors = Tetreau G, Andreeva EA, Banneville AS, De Zitter E, Colletier JP | title = How Does Bacillus thuringiensis Crystallize Such a Large Diversity of Toxins? | journal = Toxins | volume = 13 | issue = 7 | pages = 443 | date = June 2021 | pmid = 34206796 | pmc = 8309854 | doi = 10.3390/toxins13070443 | doi-access = free }}

File:Ovitrap-Ticino.jpg collects eggs from mosquitoes. The brown granules in the water are a B. t. israelensis preparation that kills hatched larvae.]]

• Biological insecticides
• Genetically modified food
• Western corn rootworm
• Cry1Ac
• Diamondback moth
• Sterile insect technique

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• {{cite journal | vauthors = de Maagd RA, Bravo A, Crickmore N | title = How Bacillus thuringiensis has evolved specific toxins to colonize the insect world | journal = Trends in Genetics | volume = 17 | issue = 4 | pages = 193–9 | date = April 2001 | pmid = 11275324 | doi = 10.1016/S0168-9525(01)02237-5 }}
• {{cite journal | vauthors = Bravo A, Gill SS, Soberón M | title = Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control | journal = Toxicon | volume = 49 | issue = 4 | pages = 423–35 | date = March 2007 | pmid = 17198720 | pmc = 1857359 | doi = 10.1016/j.toxicon.2006.11.022 }}
• {{cite journal | vauthors = Pigott CR, Ellar DJ | title = Role of receptors in Bacillus thuringiensis crystal toxin activity | journal = Microbiology and Molecular Biology Reviews | volume = 71 | issue = 2 | pages = 255–81 | date = June 2007 | pmid = 17554045 | pmc = 1899880 | doi = 10.1128/MMBR.00034-06 }}
• {{cite journal | vauthors = Tabashnik BE, Van Rensburg JB, Carrière Y | title = Field-evolved insect resistance to Bt crops: definition, theory, and data | journal = Journal of Economic Entomology | volume = 102 | issue = 6 | pages = 2011–25 | date = December 2009 | pmid = 20069826 | doi = 10.1603/029.102.0601 | s2cid = 2325989 }}

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• {{cite web | url = http://npic.orst.edu/factsheets/BTgen.pdf | title = Bacillus thuringiensis General Fact Sheet | work = National Pesticide Information Center }}
• {{cite web | url = http://npic.orst.edu/factsheets/archive/BTtech.pdf | title = Bacillus thuringiensis Technical Fact Sheet | work = National Pesticide Information Center }}
• {{cite web | url = http://www.gmo-safety.eu/database/1004.breakdown-toxin-effects-micro-organisms-soil.html | title = Breakdown of the Bt toxin and effects on the soil quality | work = Research project and results | archive-url = https://web.archive.org/web/20110716052010/http://www.gmo-safety.eu/database/1004.breakdown-toxin-effects-micro-organisms-soil.html | archive-date = 2011-07-16 }}
• {{cite web | url = http://cfs.nrcan.gc.ca/subsite/glfc-bacillus-thuringiensis/bacillus-thuringiensis | title = The Bacillus thuringiensis Toxin Specificity Database | work = Natural Resources Canada | archive-url = https://web.archive.org/web/20090217033726/http://cfs.nrcan.gc.ca/subsite/glfc-bacillus-thuringiensis/bacillus-thuringiensis | archive-date = 2009-02-17 }}
• {{cite web | url = https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=1428 | title = Bacillus thuringiensis Taxonomy | work = NIH }}
• {{cite web | url = http://patricbrc.org/portal/portal/patric/Taxon?cType=taxon&cId=1428 | title = Bacillus thuringiensis] genomes and related information | work = PATRIC, a Bioinformatics Resource Center | publisher = NIAID | archive-url = https://web.archive.org/web/20110727170358/http://patricbrc.org/portal/portal/patric/Taxon?cType=taxon&cId=1428 | archive-date = 2011-07-27 }}
• {{cite web | url = http://www.mendeley.com/groups/1296883/becon | work = bEcon | title = Economics literature about the impacts of genetically engineered (GE) crops in developing economies }}
• {{cite web | url = http://bacdive.dsmz.de/index.php?search=1006&submit=Search | title = Type strain of Bacillus thuringiensis | work = Bac Dive - the Bacterial Diversity Metadatabase }}

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thuringiensis

Category:Biopesticides

Category:Genetically modified organisms in agriculture

Category:Bacteria described in 1915