Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1784852807957872640 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9762135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT chowooyoung nacylamidesfromneisseriameningitidisandtheirroleinsphingosinereceptorsignaling AT yorkautumng nacylamidesfromneisseriameningitidisandtheirroleinsphingosinereceptorsignaling AT wangrurun nacylamidesfromneisseriameningitidisandtheirroleinsphingosinereceptorsignaling AT wychethomasp nacylamidesfromneisseriameningitidisandtheirroleinsphingosinereceptorsignaling AT piizzigrazia nacylamidesfromneisseriameningitidisandtheirroleinsphingosinereceptorsignaling AT flavellricharda nacylamidesfromneisseriameningitidisandtheirroleinsphingosinereceptorsignaling AT crawfordjasonm nacylamidesfromneisseriameningitidisandtheirroleinsphingosinereceptorsignaling |