Peptide YY: a Paneth cell antimicrobial peptide that maintains Candida gut commensalism.

The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility, while some regulate the microbiota. We report peptide YY (PYY1-36), but not endocrine PYY3-36, is an antimicrobial peptide (AMP) expressed by gut epithelial Paneth Cells (PC). PC-PYY has limited antibacterial activity, but shows selective activity against virulent hyphal, but not yeast forms, of Candida albicans. 5 PC-PYY is a cationic molecule that interacts with the anionic surfaces of fungal hyphae to cause membrane disruption and transcriptional reprogramming to maintain the yeast phenotype of the fungus. PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity. Hence, PC-PYY acts as a selective antifungal AMP that contributes to the maintenance of gut fungal commensalism. In vitro cultures of C. albicans in yeast and hyphae forms were treated with a small peptide, PYY1-36 (30µM), or saline vehicle control and harvested for RNA after 4 h of treatment. (Yeast_ctrl=yeast+saline, Yeast_PYY=Yeast+PYY1-36, hyphae_ctrl=hyphae+saline, hyphae_PYY=hyphae + PYY1-36)