Biosynthetic flexibility of Pseudomonas aeruginosa leads to hydroxylated 2-alkylquinolones with proinflammatory host response.
Commun Chem
; 6(1): 138, 2023 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-37400564
ABSTRACT
The human pathogen Pseudomonas aeruginosa produces various 4(1H)-quinolones with diverse functions. Among these, 2-nonyl-4(1H)-quinolone (NQ) and its N-oxide (NQNO) belong to the main metabolites. Their biosynthesis involves substrates from the fatty acid metabolism and we hypothesized that oxidized fatty acids could be responsible for a so far undetected class of metabolites. We developed a divergent synthesis strategy for 2'-hydroxy (2'-OH) and 2'-oxo- substituted quinolones and N-oxides and demonstrated for the first time that 2'-OH-NQ and 2'-OH-NQNO but not the corresponding 2'-oxo compounds are naturally produced by PAO1 and PA14 strains of P. aeruginosa. The main metabolite 2'-OH-NQ is produced even in concentrations comparable to NQ. Exogenous availability of ß-hydroxydecanoic acid can further increase the production of 2'-OH-NQ. In contrast to NQ, 2'-OH-NQ potently induced the cytokine IL-8 in a human cell line at 100 nм, suggesting a potential role in host immune modulation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Commun Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Áustria