Altered expression profile of mycobacterial surface glycopeptidolipids following treatment with the antifungal azole inhibitors econazole and clotrimazole
Altered expression profile of mycobacterial surface glycopeptidolipids following treatment with the antifungal azole inhibitors econazole and clotrimazole
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DOI：
10.1099/mic.0.27938-0
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发表时间：
2005-06-01
期刊：
影响因子：
2.8
通讯作者：
Besra, GS
中科院分区：
文献类型：
--
作者：
Burguière, A;Hitchen, PG;Besra, GS
唑类抗真菌药物益康唑和克霉唑是已知的细胞色素P450酶抑制剂。本研究表明，这些药物是分枝杆菌生长的有效抑制剂，并且比异烟肼和乙硫酰胺这两种已建立的抗分枝杆菌药物对耻垢分枝杆菌更有效。几种非结核分枝杆菌，包括鸟分枝杆菌-细胞内复合体（MAC）的致病性成员和快速生长的腐生菌耻垢分枝杆菌，产生一系列血清特异性（ss）和非血清特异性（ns）糖肽类脂（GPLs）。GPL的生物合成研究已经进行了几年，但仍未完全阐明。作者在这里证明，econazole和clotrimazole抑制垢垢分枝杆菌GPL的生物合成，特别是，clotrimazole抑制垢垢分枝杆菌中发现的所有四种类型的nsgpl，提示其生物合成途径中的早期和共同靶点。总之，这些数据表明，在GPL生物合成过程中，氮唑特异性靶标（很可能是细胞色素P450）可能参与了n -酰基链的羟基化。唑类抗真菌药物及其潜在衍生物可能代表了一个有趣的抗分枝杆菌药物的新范围，特别是针对机会性人类病原体，包括MAC， M. scrofulaceum， M. peregrinum， M. chelonae和M.脓肿。
The azole antifungal drugs econazole and clotrimazole are known cytochrome P450 enzyme inhibitors. This study shows that these drugs are potent inhibitors of mycobacterial growth and are more effective against Mycobacterium smegmatis than isoniazid and ethionamide, two established anti-mycobacterial drugs. Several non-tuberculous mycobacteria, including the pathogenic members of the Mycobacterium avium-intracellulare complex (MAC) and the fast-growing saprophytic organism M. smegmatis, produce an array of serovar-specific (ss) and non-serovar-specific (ns) glycopeptidolipids (GPLs). GPL biosynthesis has been investigated for several years but has still not been fully elucidated, The authors demonstrate here that econazole and clotrimazole inhibit GPL biosynthesis in M. smegmatis, In particular, clotrimazole inhibits all four types of nsGPLs found in M. smegmatis, suggesting an early and common target within their biosynthetic pathway. Altogether, the data suggest that an azole-specific target, most likely a cytochrome P450, may be involved in the hydroxylation of the N-acyl chain in GPL biosynthesis. Azole antifungal drugs and potential derivatives could represent an interesting new range of anti-mycobacterial drugs, especially against opportunistic human pathogens including MAC, M. scrofulaceum, M. peregrinum, M. chelonae and M. abscessus.