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Molecules 2013, 18(2), 1728-1740; doi:10.3390/molecules18021728

Article

Anti-Mycobacterial Activity of Marine Fungus-Derived 4-Deoxybostrycin and Nigrosporin

Cong Wang ^1,2,† , Juan Wang ^1,2,† , Yuhong Huang ^1,2,† , Hong Chen ^2,3 , Yan Li ^1,2 , Lili Zhong ^2,3 , Yi Chen ^1,2 , Shengping Chen ² , Jun Wang ^2,4 , Juling Kang ⁵ , Yi Peng ^1,2 , Bin Yang ^2,3 , Yongcheng Lin ^2,3 , Zhigang She ^2,3,*  and Xiaomin Lai ^1,2,*

¹ Department of Microbiology, Gangdong Provincial Research Centre for Severe Infectious Disease Prevention and Control Technology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China ² China Ministry of Education Key Laboratory of Tropical Diseases Control, Gangdong Provincial Department of Education Key Laboratory of Functional Molecules from Marine Microorganisms, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China ³ School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, Guangdong, China ⁴ School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China ⁵ Department of Pathology, the First Affiliated Hospital of Jinan University (Guangzhou Overseas Chinese Hospital), Guangzhou 510630, Guangdong, China ^† These authors contributed equally to this work.

* Authors to whom correspondence should be addressed.

Received: 28 November 2012; in revised form: 17 December 2012 / Accepted: 15 January 2013 / Published: 29 January 2013

(This article belongs to the Section Natural Products)

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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.

Keywords: anti-mycobacterial activity; 4-deoxybostrycin; differentially expressed genes

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