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

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.

Structural Element of Vitamin U‐Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections

“…G 2 ‐PL‐1 with lysine residue showed MIC values of 8 and 16 μg mL −1 against S. aureus and E. coli . To investigate the effect of sulfonium and ‐NH 3 + groups on antibacterial properties, an electrostatic potential analysis was conducted using DMol 3 calculation [35] . The positive charge in the ‐NH 3 + is distributed on the hydrogen atoms and facile departure (Figure 1d).…”

“…To investigate the effect of sulfonium and -NH 3 + groups on antibacterial properties, an electrostatic potential analysis was conducted using DMol 3 calculation. [35] The positive charge in the -NH 3…”

Screening and investigation of a short antimicrobial peptide: AVGAV

“…and some published scientific literature. [10][11][12] The researchers initially designed a peptide chain with a balance between hydrophilicity and hydrophobicity, 13 with an overall positive charge, and then randomly arranged and combined the amino acids that make up the peptide chain; finally, a peptide library was built.…”

The antimicrobial peptide database is 20 years old: Recent developments and future directions

“…The growing research on microbiota added a new dimension to AMP research due to its connection with a variety of human diseases (Wang et al, 2023; Wehkamp et al, 2005). AMPs are important players that shape microbiota (de San et al, 2022; Pierre et al, 2023; Snelders et al, 2021). Remarkably, a Paneth cell peptide YY was able to selectively eliminate pathogenic hyphae but not the commensal yeast form of Candida albicans (Pierre et al, 2023).…”

“…AMPs are important players that shape microbiota (de San et al, 2022; Pierre et al, 2023; Snelders et al, 2021). Remarkably, a Paneth cell peptide YY was able to selectively eliminate pathogenic hyphae but not the commensal yeast form of Candida albicans (Pierre et al, 2023). The omic approaches have also been utilized to AMP discovery (Bishop et al, 2017; Conlon et al, 2006; Lai, 2010; Moyer et al, 2021).…”