<i>Bacillus thuringiensis</i> Cry1A toxins divert progenitor cells toward enteroendocrine fate by decreasing cell adhesion with intestinal stem cells
- Others:
- Institut Sophia Agrobiotech (ISA) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE)-Université Côte d'Azur (UCA)
- azm Center for research in biotechnology and its applications ; Université Libanaise
- Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl) ; Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
- Département des Alpes-Maritimes, by the Institut Olga Triballat (PR2016-19) and by the ANSES PNR-EST & ECOPHYTO II (EST-2017-2021). RJ was funded by the association AZM & SAADE (Lebanon) and Université Côte d'Azur (ATER). RL was funded by the Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche (MESR) and a grant from the Fondation pour la Recherche Médicale (FRM).
- ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)
- ANR-13-CESA-0003,ImBio,Impacts d'une intoxication chronique par des bioinsecticides Bt k sur l'homéostasie intestinale et la réponse immunitaire: des insectes aux mammifères(2013)
Description
Bacillus thuringiensis subsp. kurstaki (Btk) is a strong pathogen toward lepidopteran larvae thanks to specific Cry toxins causing leaky gut phenotypes. Hence, Btk and its toxins are used worldwide as microbial insecticide and in genetically modified crops, respectively, to fight crop pests. However, Btk belongs to the B. cereus group, some strains of which are well known human opportunistic pathogens. Therefore, ingestion of Btk along with food may threaten organisms not susceptible to Btk infection. Here we show that Cry1A toxins induce enterocyte death and intestinal stem cell (ISC) proliferation in the midgut of Drosophila melanogaster, an organism nonsusceptible to Btk. Surprisingly, a high proportion of the ISC daughter cells differentiate into enteroendocrine cells instead of their initial enterocyte destiny. We show that Cry1A toxins weaken the Cadherin-dependent adherens junction between the ISC and its immediate daughter progenitor, leading the latter to adopt an enteroendocrine fate. Hence, though not lethal to nonsusceptible organisms, Cry toxins can interfere with conserved cell adhesion mechanisms, thereby disrupting intestinal homeostasis and enteroendocrine functions.
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-03822210
- URN
- urn:oai:HAL:hal-03822210v1
- Origin repository
- UNICA