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Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota
The flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038955/ https://www.ncbi.nlm.nih.gov/pubmed/33484270 http://dx.doi.org/10.1007/s00018-020-03755-w |
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author | Murtas, Giulia Sacchi, Silvia Tedeschi, Gabriella Maffioli, Elisa Notomista, Eugenio Cafaro, Valeria Abbondi, Monica Mothet, Jean-Pierre Pollegioni, Loredano |
author_facet | Murtas, Giulia Sacchi, Silvia Tedeschi, Gabriella Maffioli, Elisa Notomista, Eugenio Cafaro, Valeria Abbondi, Monica Mothet, Jean-Pierre Pollegioni, Loredano |
author_sort | Murtas, Giulia |
collection | PubMed |
description | The flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal d-amino acids to generate hydrogen peroxide (H(2)O(2)), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1–16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-020-03755-w. |
format | Online Article Text |
id | pubmed-8038955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-80389552021-04-27 Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota Murtas, Giulia Sacchi, Silvia Tedeschi, Gabriella Maffioli, Elisa Notomista, Eugenio Cafaro, Valeria Abbondi, Monica Mothet, Jean-Pierre Pollegioni, Loredano Cell Mol Life Sci Original Article The flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal d-amino acids to generate hydrogen peroxide (H(2)O(2)), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1–16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-020-03755-w. Springer International Publishing 2021-01-23 2021 /pmc/articles/PMC8038955/ /pubmed/33484270 http://dx.doi.org/10.1007/s00018-020-03755-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Murtas, Giulia Sacchi, Silvia Tedeschi, Gabriella Maffioli, Elisa Notomista, Eugenio Cafaro, Valeria Abbondi, Monica Mothet, Jean-Pierre Pollegioni, Loredano Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota |
title | Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota |
title_full | Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota |
title_fullStr | Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota |
title_full_unstemmed | Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota |
title_short | Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota |
title_sort | antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038955/ https://www.ncbi.nlm.nih.gov/pubmed/33484270 http://dx.doi.org/10.1007/s00018-020-03755-w |
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