Peptide YY: A Paneth cell antimicrobial peptide that maintains Candida gut commensalism.
Joseph F PierreBrian M PetersDiana La TorreAshley M SidebottomYun TaoXiaorong ZhuCandace M ChamLing WangAmal KambalKatharine G HarrisJulian F SilvaOlga ZaborinaJohn C AlverdyHerbert HerzogJessica WitchleySuzanne M NobleVanessa A LeoneEugene B ChangPublished in: Science (New York, N.Y.) (2023)
The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility whereas others regulate the microbiota. We have found that peptide YY (PYY 1-36 ), but not endocrine PYY 3-36 , acts as an antimicrobial peptide (AMP) expressed by gut epithelial paneth cells (PC). PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity. Although PC-PYY shows some antibacterial activity, it displays selective antifungal activity against virulent Candida albicans hyphae-but not the yeast form. PC-PYY is a cationic molecule that interacts with the anionic surfaces of fungal hyphae to cause membrane disruption and transcriptional reprogramming that selects for the yeast phenotype. Hence, PC-PYY is an antifungal AMP that contributes to the maintenance of gut fungal commensalism.