Bacillus thuringiensis Cry1A toxins divert progenitor cell fate toward enteroendocrine lineage by diminishing cell adhesion with intestinal stem cells

Bacillus thuringiensis subsp kurstaki ( Btk ) is a strong pathogen toward lepidopteran larvae thanks to specific Cry toxins causing leaky gut phenotypes. Hence, Btk is used worldwide as microbial insecticide to fight crop pests. Btk ingested along with food could also threat gut integrity of organisms insensitive 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 ISC's daughter cells differentiates into enteroendocrine cells instead of their initial enterocyte destiny. We show that Cry1A toxins are activated in the midgut and weakened 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 non-susceptible organisms, Cry toxins can interfere with conserved cell adhesion mechanisms, thereby disrupting intestinal homeostasis and physiology. ### Competing Interest Statement The authors have declared no competing interest.