<i>Bacillus thuringiensis</i> toxins divert progenitor cells toward enteroendocrine fate by decreasing cell adhesion with intestinal stem cells in <i>Drosophila</i>.

Abstract

<i>Bacillus thuringiensis</i> subsp. <i>kurstaki</i> (<i>Btk</i>) is a strong pathogen toward lepidopteran larvae thanks to specific Cry toxins causing leaky gut phenotypes. Hence, <i>Btk</i> and its toxins are used worldwide as microbial insecticide and in genetically modified crops, respectively, to fight crop pests. However, <i>Btk</i> belongs to the <i>B. cereus</i> group, some strains of which are well known human opportunistic pathogens. Therefore, ingestion of <i>Btk</i> along with food may threaten organisms not susceptible to <i>Btk</i> infection. Here we show that Cry1A toxins induce enterocyte death and intestinal stem cell (ISC) proliferation in the midgut of <i>Drosophila melanogaster</i>, an organism non-susceptible to <i>Btk</i>. 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.