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, Xiaorong Zhu, Candace M. Cham, Ling Wang, Amal Kambal, Katharine G. Harris, Julian Furtado Silva,

Science · 2023 · 93 citations · 28 references

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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.

References

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