- Pierre, Joseph;
- Peters, Brian;
- La Torre, Diana;
- Sidebottom, Ashley;
- Tao, Yun;
- Zhu, Xiaorong;
- Cham, Candace;
- Wang, Ling;
- Kambal, Amal;
- Harris, Katharine;
- Silva, Julian;
- Zaborina, Olga;
- Alverdy, John;
- Herzog, Herbert;
- Witchley, Jessica;
- Leone, Vanessa;
- Chang, Eugene;
- Noble, Suzanne
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 (PYY1-36), but not endocrine PYY3-36, 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.