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

作者：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 Y. Zaborina, John C. Alverdy, Herbert Herzog, Jessica N. Witchley, Suzanne M. Noble, Vanessa Leone, Eugene B. Chang · 发表于：Science · 年份：2023 · DOI：10.1126/science.abq3178 · 被引用次数：98 · 研究领域：Antimicrobial Peptides and Activities、Probiotics and Fermented Foods、Gut microbiota and health

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.