Peptide YY: A Paneth cell antimicrobial peptide that maintains <i>Candida</i> gut commensalism
Joseph F. Pierre, Brian M. Peters, Diana La Torre, Ashley M. Sidebottom, Yiwei Tao, Xiaorong Zhu, Candace M. Cham, Ling Wang, Amal Kambal, Katharine G. Harris, Julian Furtado Silva, Olga Zaborina, John C. Alverdy, Herbert Herzog, Jessica N. Witchley, Suzanne M. Noble, Vanessa Leone, Eugene B. Chang
Abstract
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.