Vibrio cholerae-Symbiont Interactions Inhibit Intestinal Repair in Drosophila

Abstract

Summary: Pathogen-mediated damage to the intestinal epithelium activates compensatory growth and differentiation repair programs in progenitor cells. Accelerated progenitor growth replenishes damaged tissue and maintains barrier integrity. Despite the importance of epithelial renewal to intestinal homeostasis, we know little about the effects of pathogen-commensal interactions on progenitor growth. We find that the enteric pathogen Vibrio cholerae blocks critical growth and differentiation pathways in Drosophila progenitors, despite extensive damage to epithelial tissue. We show that the inhibition of epithelial repair requires interactions between the Vibrio cholerae type six secretion system and a community of common symbiotic bacteria, as elimination of the gut microbiome is sufficient to restore homeostatic growth in infected intestines. This work highlights the importance of pathogen-symbiont interactions for intestinal immune responses and outlines the impact of the type six secretion system on pathogenesis. : Fast et al. demonstrate that intestinal infection with Vibrio cholerae with a type six secretion system disrupts intestinal homeostasis and blocks growth and repair pathways in intestinal progenitors. The inhibition of epithelial regeneration requires interactions between Vibrio cholerae and a complex community of common symbiotic bacteria in the fly gut. Keywords: microbiome, type VI secretion system, intestinal progenitors, repair, IMD, Vibrio cholera, Drosophila