RRC ID |
64096
|
著者 |
Arai MA, Ebihara I, Makita Y, Hara Y, Yaguchi T, Ishibashi M.
|
タイトル |
Isolation of nocobactin NAs as Notch signal inhibitors from Nocardia farcinica, a possibility of invasive evolution.
|
ジャーナル |
J Antibiot (Tokyo)
|
Abstract |
Notch signaling inhibitors with the potential of immune suppressor production by pathogenic bacteria for easy host infection were searched from extracts of Nocardia sp. Nocobactin NA-a (compound 1) and nocobactin NA-b (compound 2), which have been suggested as pathogenesis factors, were isolated from N. farcinica IFM 11523 isolated from the sputum of a Japanese patient with chronic bronchitis. Compounds 1 and 2 showed Notch inhibitory activities with IC50 values of 12.4 and 17.6 μM, respectively. Compound 1 and 2 decreased of Notch1 protein, Notch intracellular domain, and hairy and enhancer of split 1, which is a Notch signaling target protein. In addition, compounds 1 and 2 showed cytotoxicity against mouse macrophage-like cell line RAW264.7 with IC50 values of 18.9 and 21.1 μM, respectively. These results suggested that the Notch inhibitors production by pathogenic bacteria may increase pathogen infectivity.
|
巻・号 |
74(4)
|
ページ |
255-259
|
公開日 |
2021-1-1
|
DOI |
10.1038/s41429-020-00393-z
|
PII |
10.1038/s41429-020-00393-z
|
PMID |
33318622
|
MeSH |
Bronchitis, Chronic / microbiology
Evolution, Molecular
Host-Pathogen Interactions*
Humans
Hydroxamic Acids / isolation & purification
Hydroxamic Acids / pharmacology
Magnetic Resonance Spectroscopy
Nocardia / growth & development
Nocardia / isolation & purification
Nocardia / metabolism
Nocardia / pathogenicity*
Nocardia Infections / microbiology*
Oxazoles / isolation & purification
Oxazoles / metabolism*
Oxazoles / pharmacology
Receptors, Notch / antagonists & inhibitors
Receptors, Notch / metabolism*
Signal Transduction
Sputum / microbiology
Virulence Factors / metabolism
Virulence Factors / pharmacology
|
IF |
2.668
|
リソース情報 |
病原真核微生物 |
Nocardia farcinica IFM 11523, IFM 645 |