A conserved, immune-regulated peritrophin promotes Vibrio cholerae colonization of the arthropod intestine

Vibrio cholerae is a human diarrheal pathogen and an estuarine organism that associates with both terrestrial and aquatic arthropods. Using the model terrestrial arthropod Drosophila melanogaster, we previously showed that V. cholerae forms a multi-layered bacterial structure called a biofilm in the arthropod intestine and activates the arthropod intestinal innate immune response. Here we show that activation of the immune response in enterocytes decreases V. cholerae colonization of the arthropod intestine, while activation of the immune response in enteroendocrine cells that express the enteroendocrine peptide tachykinin (Tk) promotes V. cholerae colonization. To uncover the basis of this observation, we measured the impact of TkRNAi on intestinal gene expression by RNA-seq analysis. In addition to increasing expression of antimicrobial peptides and lipases, Tk activated the expression of chitinases and chitin-binding proteins. These proteins interact with chitin fibrils in the peritrophic matrix (PM), a protective coating that overlies the arthropod intestinal epithelium. One of these Tk-activated PM components, the small, secreted chitin-binding protein Peritrophin 15a (Peri-15a), is essential for robust V. cholerae colonization of the gut. Homologs of Peri-15a are widespread in both terrestrial and aquatic organisms including marine non-biting midges, marine copepods, rotifers, and cyanobacteria. We propose that Peri-15a and its homologs, found in the intestines of diverse arthropods, either serves as a receptor or reveals a PM epitope that promotes V. cholerae attachment to the intestinal surface. Therefore, activation of the enteroendocrine cell intestinal innate immune response by V. cholerae may, in fact, represent a colonization strategy.