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Peptide YY: A Paneth cell antimicrobial peptide that maintains Candida gut commensalism. 2023
Joseph F Pierre, and
Brian M Peters, and
Diana La Torre, and
Ashley M Sidebottom, and
Yun Tao, and
Xiaorong Zhu, and
Candace M Cham, and
Ling Wang, and
Amal Kambal, and
Katharine G Harris, and
Julian F Silva, and
Olga Zaborina, and
John C Alverdy, and
Herbert Herzog, and
Jessica Witchley, and
Suzanne M Noble, and
Vanessa A Leone, and
Eugene B Chang
Department of Medicine, University of Chicago, Chicago, IL, USA.
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.
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