Isolation of nocobactin NAs as Notch signal inhibitors from Nocardia farcinica, a possibility of invasive evolution

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 mu M, 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 mu M, respectively. These results suggested that the Notch inhibitors production by pathogenic bacteria may increase pathogen infectivity.

Automated summary

In this study, Notch signaling inhibitors were identified from extracts of Nocardia sp., with compound 1 and compound 2 showing Notch inhibitory activities. These compounds also exhibited cytotoxicity against a mouse macrophage-like cell line. The results suggest that production of Notch inhibitors by pathogenic bacteria may enhance pathogen infectivity.