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N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling

Neisseria meningitidis is a Gram-negative opportunistic pathogen that is responsible for causing human diseases with high mortality, such as septicemia and meningitis. The molecular mechanisms N. meningitidis employ to manipulate the immune system, translocate the mucosal and blood-brain barriers, a...

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Autores principales: Cho, Wooyoung, York, Autumn G., Wang, Rurun, Wyche, Thomas P., Piizzi, Grazia, Flavell, Richard A., Crawford, Jason M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762135/
https://www.ncbi.nlm.nih.gov/pubmed/36112057
http://dx.doi.org/10.1002/cbic.202200490
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author Cho, Wooyoung
York, Autumn G.
Wang, Rurun
Wyche, Thomas P.
Piizzi, Grazia
Flavell, Richard A.
Crawford, Jason M.
author_facet Cho, Wooyoung
York, Autumn G.
Wang, Rurun
Wyche, Thomas P.
Piizzi, Grazia
Flavell, Richard A.
Crawford, Jason M.
author_sort Cho, Wooyoung
collection PubMed
description Neisseria meningitidis is a Gram-negative opportunistic pathogen that is responsible for causing human diseases with high mortality, such as septicemia and meningitis. The molecular mechanisms N. meningitidis employ to manipulate the immune system, translocate the mucosal and blood-brain barriers, and exert virulence are largely unknown. Human-associated bacteria encode a variety of bioactive small molecules with growing evidence for N-acyl amides as being important signaling molecules. However, only a small fraction of these metabolites has been identified from the human microbiota thus far. Here, we heterologously expressed an N-acyltransferase encoded in the obligate human pathogen N. meningitidis and identified 30 N-acyl amides with representative members serving as agonists of the G-protein coupled receptor (GPCR) S1PR4. During this process, we also characterized two mammalian N-acyl amides derived from the bovine medium. Both groups of metabolites suppress anti-inflammatory interleukin-10 signaling in human macrophage cell types, but they also suppress the pro-inflammatory interleukin-17A+ population in T(H)17-differentiated CD4(+) T cells.
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spelling pubmed-97621352022-12-19 N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling Cho, Wooyoung York, Autumn G. Wang, Rurun Wyche, Thomas P. Piizzi, Grazia Flavell, Richard A. Crawford, Jason M. Chembiochem Article Neisseria meningitidis is a Gram-negative opportunistic pathogen that is responsible for causing human diseases with high mortality, such as septicemia and meningitis. The molecular mechanisms N. meningitidis employ to manipulate the immune system, translocate the mucosal and blood-brain barriers, and exert virulence are largely unknown. Human-associated bacteria encode a variety of bioactive small molecules with growing evidence for N-acyl amides as being important signaling molecules. However, only a small fraction of these metabolites has been identified from the human microbiota thus far. Here, we heterologously expressed an N-acyltransferase encoded in the obligate human pathogen N. meningitidis and identified 30 N-acyl amides with representative members serving as agonists of the G-protein coupled receptor (GPCR) S1PR4. During this process, we also characterized two mammalian N-acyl amides derived from the bovine medium. Both groups of metabolites suppress anti-inflammatory interleukin-10 signaling in human macrophage cell types, but they also suppress the pro-inflammatory interleukin-17A+ population in T(H)17-differentiated CD4(+) T cells. 2022-11-18 2022-10-13 /pmc/articles/PMC9762135/ /pubmed/36112057 http://dx.doi.org/10.1002/cbic.202200490 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Cho, Wooyoung
York, Autumn G.
Wang, Rurun
Wyche, Thomas P.
Piizzi, Grazia
Flavell, Richard A.
Crawford, Jason M.
N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
title N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
title_full N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
title_fullStr N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
title_full_unstemmed N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
title_short N-acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
title_sort n-acyl amides from neisseria meningitidis and their role in sphingosine receptor signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762135/
https://www.ncbi.nlm.nih.gov/pubmed/36112057
http://dx.doi.org/10.1002/cbic.202200490
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