Abstract
4-Deoxybostrycin is a natural anthraquinone compound isolated from the Mangrove endophytic fungus Nigrospora sp. collected from the South China Sea. Nigrosporin is the deoxy-derivative of 4-deoxybostrycin. They were tested against mycobacteria, especially Mycobacterium tuberculosis. In the Kirby-Bauer disk diffusion susceptibility test, they both had inhibition zone sizes of over 25 mm. The results of the absolute concentration susceptibility test suggested that they had inhibitory effects against mycobacteria. Moreover, 4-deoxybostrycin exhibited good inhibition which was even better than that of first line anti-tuberculosis (TB) drugs against some clinical multidrug-resistant (MDR) M. tuberculosis strains. The gene expression profile of M. tuberculosis H37Rv after treatment with 4-deoxybostrycin was compared with untreated bacteria. One hundred and nineteen out of 3,875 genes were significantly different in M. tuberculosis exposed to 4-deoxybostrycin from control. There were 46 functionally known genes which are involved in metabolism, information storage and processing and cellular processes. The differential expressions of six genes were further confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The present study provides a useful experiment basis for exploitation of correlative new drugs against TB and for finding out new targets of anti-mycobacterial therapy.
Highlights
Tuberculosis (TB) remains an international public health burden around the World
4-deoxybostrycin and nigrosporin were isolated from the mangrove endophytic fungus Nigrospora sp. collected from the South China Sea as previously reported [8,9]
The in vitro anti-mycobacterial activity of the compounds was first screened with the Kirby-Bauer disk diffusion susceptibility test. 4-Deoxybostrycin and nigrosporin showed an inhibition zone size of 30 mm and
Summary
Tuberculosis (TB) remains an international public health burden around the World. Current global estimates indicate that one third of the global population was infected with TB. 0.35 million deaths from HIV-associated TB [1]. The growing problem of drug-resistance combined with the deadly link between TB and HIV infection underscore the urgent need for new anti-TB agents. 4-Deoxybostrycin (Figure 1A), a natural anthraquinone compound, was first isolated from the fungus. Nigrosporin (Figure 1B) is the deoxy-derivative of 4-deoxybostrycin. It was a natural product which was first isolated from the fungus Nigrospora oryzae. We obtained 4-deoxybostrycin and nigrosporin isolated from the fungus. Its anti-mycobacterial activity is not well investigated. We tested it and its derivative’s anti-mycobacterial activity in vitro. We first screened and quantitated the anti-mycobacterial activity of the compound and its derivative with the Kirby-Bauer disk diffusion susceptibility test and the absolute concentration susceptibility test respectively. We detected the differential expression of M. tuberculosis genes after treatment with 4-deoxybostrycin by gene chips and confirmed the results with quantitative real-time polymerase chain reaction (qRT-PCR) experiments
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