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首页> 外文期刊>ACS Omega >Imidazoles Induce Reactive Oxygen Species in Mycobacterium tuberculosis Which Is Not Associated with Cell Death
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Imidazoles Induce Reactive Oxygen Species in Mycobacterium tuberculosis Which Is Not Associated with Cell Death

机译:咪唑诱导与细胞死亡无关的结核分枝杆菌中的活性氧

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Azoles are a class of antimicrobial drugs used clinically to treat yeast and fungal infections. Against pathogenic yeast and fungi, azoles act by inhibiting the activity of the cytochrome P450 Cyp51, which is involved in the synthesis of a critical component of the yeast and fungal cell membrane. Azoles have antibacterial activity, including against mycobacteria, but the basis for this activity is not well-understood. We demonstrated that imidazoles are bactericidal to Mycobacterium tuberculosis . A marked increase in reactive oxygen species (ROS) was observed within imidazole-treated M. tuberculosis . The generation of ROS did not appear to be related to the mechanism of killing of imidazoles, as the addition of antioxidants or altered expression of detoxifying enzymes had no effect on growth. We examined the metabolic changes induced by econazole treatment in both wild-type and econazole-resistant mutant strains of M. tuberculosis . Econazole treatment induced changes in carbohydrates, amino acids, and energy metabolism in both strains. Notably, the untreated mutant strain had a metabolic profile similar to the wild-type drug-treated cells, suggesting that adaptation to similar stresses may play a role in econazole resistance.
机译:唑是临床上用于治疗酵母和真菌感染的一类抗菌药物。吡咯类抗病原性酵母和真菌的作用是抑制细胞色素P450 Cyp51的活性,该酶参与酵母和真菌细胞膜关键成分的合成。唑具有抗菌活性,包括针对分枝杆菌的抗菌活性,但是这种活性的基础尚不为人所知。我们证明了咪唑类对结核分枝杆菌具有杀菌作用。在咪唑处理的M中观察到活性氧(ROS)的显着增加。肺结核。 ROS的产生似乎与杀灭咪唑的机制无关,因为添加抗氧化剂或改变解毒酶的表达对生长没有影响。我们检查了野生型和抗药性的iM突变菌株中,通过益康唑处理诱导的代谢变化。肺结核。益康唑处理可诱导两种菌株的碳水化合物,氨基酸和能量代谢发生变化。值得注意的是,未经处理的突变菌株具有与野生型药物处理细胞相似的代谢特征,这表明对相似压力的适应可能在益康唑耐药性中起作用。

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