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

Autor: Cho W; Department of Chemistry, Yale University, New Haven, CT, USA.; Institute of Biomolecular Design & Discovery, Yale University, West Haven, CT, USA., York AG; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Wang R; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, USA., Wyche TP; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, USA., Piizzi G; Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, USA., Flavell RA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA., Crawford JM; Department of Chemistry, Yale University, New Haven, CT, USA.; Institute of Biomolecular Design & Discovery, Yale University, West Haven, CT, USA.; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2022 Nov 18; Vol. 23 (22), pp. e202200490. Date of Electronic Publication: 2022 Oct 13.
DOI: 10.1002/cbic.202200490
Abstrakt: 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 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: