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

• 成果类型: Article
• 署名作者: Pierre, Joseph F.; Peters, Brian M.; La Torre, Diana; Sidebottom, Ashley M.; Tao, Yun; Zhu, Xiaorong; Cham, Candace M.; Wang, Ling; Kambal, Amal; Harris, Katharine G.; Silva, Julian F.; Zaborina, Olga; Alverdy, John C.; Herzog, Herbert; Witchley, Jessica; Noble, Suzanne M.; Leone, Vanessa A.; Chang, Eugene B.
• 署名单位: University of Chicago; University of Wisconsin System; University of Wisconsin Madison; University of Tennessee System; University of Tennessee Health Science Center; University of Chicago; Garvan Institute of Medical Research; University of California System; University of California San Francisco; University of California System; University of California Berkeley; University of Wisconsin System; University of Wisconsin Madison
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13909
• DOI: 10.1126/science.abq3178
• 发表日期: 2023-08-04
• 页码: 502-508
• 关键词: structure prediction; web server; albicans; pyy; mucin; rat; iv

摘要

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.