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In Vitro Effect of DFC-2 on Mycolic Acid Biosynthesis in Mycobacterium tuberculosis

김용식|이기인|류지원|남궁우|송호연|김수경|서훈희|Hafij Al Mahmud|Md Imtiazul Islam|이병의
한국미생물·생명공학회 (The Korean Society For Microbiology And Biotechnology)|2017|Journal of Microbiology and Biotechnology|제27권 제11호|pp. 1932-1941

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키워드

M. tuberculosisDFC-2mycolic acid
주제분류생물학

초록

DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2’,3’- d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to 0.39 μg/ml, DFC-2 inhibited both drugsusceptible and –resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2’s action in M. tuberculosis. The most affected functional gene category was “lipid biosynthesis,” which is involved in mycolic acid synthesis. The decrease in transcription of genes related to mycolic acid synthesis was confirmed by RT-PCR. Furthermore, we found that DFC-2 triggered a reduction in mycolic acid levels, showing a similar pattern to that of mycolic acid synthesis inhibitor isoniazid. These results may explain how this compound kills mycobacteria efficiently by inhibiting mycolic acid synthesis.

Abstract

DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2’,3’- d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to 0.39 μg/ml, DFC-2 inhibited both drugsusceptible and –resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2’s action in M. tuberculosis. The most affected functional gene category was “lipid biosynthesis,” which is involved in mycolic acid synthesis. The decrease in transcription of genes related to mycolic acid synthesis was confirmed by RT-PCR. Furthermore, we found that DFC-2 triggered a reduction in mycolic acid levels, showing a similar pattern to that of mycolic acid synthesis inhibitor isoniazid. These results may explain how this compound kills mycobacteria efficiently by inhibiting mycolic acid synthesis.

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