Azole antifungals are potent inhibitors of cytochrome P450 mono-oxygenases and bacterial growth in mycobacteria and streptomycetes
Azole antifungals are potent inhibitors of cytochrome P450 mono-oxygenases and bacterial growth in mycobacteria and streptomycetes
复制标题
DOI：
10.1099/00221287-148-10-2937
复制
发表时间：
2002-10-01
期刊：
影响因子：
2.8
通讯作者：
Munro, AW
中科院分区：
文献类型：
--
作者：
McLean, KJ;Marshall, KR;Munro, AW
结核分枝杆菌的基因组序列揭示了该生物体内存在20种不同的细胞色素P450单加氧酶（P450），并且其他分枝杆菌和天蓝色链霉菌的后续基因组序列表明这些放线菌也具有大量的P450互补物，指出这些酶的重要生理作用。放线菌P450包括14 α-甾醇脱甲基酶的同系物，14 α-甾醇脱甲基酶是酵母和真菌中唑类药物的靶标。以前，这种类型的P450被认为是细菌中不存在的。当在生长培养基中以低浓度存在时，唑类抗真菌药物被证明是耻垢分枝杆菌和链霉菌菌株生长的有效抑制剂，这表明这些细菌中的一个或多个P450是可行的药物靶标。益康唑和克霉唑对M.磺胺甲基嘧啶（MIC值
The genome sequence of Mycobacterium tuberculosis has revealed the presence of 20 different cytochrome P450 mono-oxygenases (P450s) within this organism, and subsequent genome sequences of other mycobacteria and of Streptomyces coelicolor have indicated that these actinomycetes also have large complements of P450s, pointing to important physiological roles for these enzymes. The actinomycete P450s include homologues of 14alpha-sterol demethylases, the targets for the azole class of drugs in yeast and fungi. Previously, this type of P450 was considered to be absent from bacteria. When present at low concentrations in growth medium, azole antifungal drugs were shown to be potent inhibitors of the growth of Mycobacterium smegmatis and of Streptomyces strains, indicating that one or more of the P450s in these bacteria were viable drug targets. The drugs econazole and clotrimazole were most effective against M. smegmatis (MIC values of