Bacillus thuringiensis toxins divert progenitor cells toward enteroendocrine fate by decreasing cell adhesion with intestinal stem cells in Drosophila

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  • Jneid, Rouba
  • Loudhaief, Rihab
  • Nathalie Zucchini-Pascal
  • Marie Paule Nawrot-Esposito
  • Arnaud Fichant
  • Raphael Rousset
  • Mathilde Bonis
  • Dani Osman
  • Armel Gallet
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 non-susceptible 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 E-Cadherin-dependent adherens junction between the ISC and its immediate daughter progenitor, leading the latter to adopt an enteroendocrine fate. Hence, although not lethal to non-susceptible organisms, Cry toxins can interfere with conserved cell adhesion mechanisms, thereby disrupting intestinal homeostasis and endocrine functions.
OriginalsprogEngelsk
Artikelnummere80179
TidsskrifteLife
Vol/bind12
Antal sider34
ISSN2050-084X
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We are grateful to all members of the BES team for fruitful discussions. We want to thank Arnaud Felten (GVB Unit, Anses Ploufragan) and Pierre-Emmanuel Douarre (SEL unit, Anses Maisons-Alfort) for their help regarding the WGS analysis of the mutant BtkCry1Ab. We also thank Laurent Ruel for providing pWA-Gal4. We are grateful to Hiroki Oda for providing the pUAST-DEFL. We thank Olivier Pierre from the microscopy platform of the Sophia Agrobiotech Institute for his help. Our thanks to the Université Côte d’Azur Office of International Scientific Visibility for English language editing of the manuscript. We also thank the Space, Environment, Risk and Resilience Academy of Université Côte d'Azur for their financial support. This work has been supported by the French government, through the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-15-IDEX-01 and through the ANR-13-CESA-0003–01, by the Région Provence Alpes Côte d'Azur, by the 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).

Publisher Copyright:
© Jneid et al.

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