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

• DOI: 10.7554/elife.80179
• Publication Date: 2023-02-27T00:00:18Z
• Authors: Rouba Jneid; Rihab Loudhaief; Nathalie Zucchini...; Marie-Paule Nawro...; Arnaud Fichant; Raphael Rousset; Mathilde Bonis; Dani Osman; Armel Gallet
• Keywords: Crops, Agricultural; 0301 basic medicine; 570; E-Cadherins; QH301-705.5; Science; Bacillus thuringiensis; [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain; intestinal stem cells.; 03 medical and health sciences; Cry1A toxins; bacillus thurigiensis; cell biology; Cell Adhesion; Animals; Biology (General); intestinal stem cells; 0303 health sciences; D. melanogaster; enteroendocrine cells; Bacillus thuringiensis Toxins; Stem Cells; Q; R; Cell Biology; Plants, Genetically Modified; [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology; Drosophila melanogaster; [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain; Medicine; [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology

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.