Mechanism of isoniazid uptake in Mycobacterium tuberculosis
Mechanism of isoniazid uptake in Mycobacterium tuberculosis
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DOI：
10.1099/00221287-144-9-2539
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发表时间：
1998-09-01
期刊：
影响因子：
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通讯作者：
Lanéelle, G
中科院分区：
文献类型：
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作者：
Bardou, F;Raynaud, C;Lanéelle, G
本文研究了结核分枝杆菌H37 Rv在不同实验条件下对异烟肼（INH）的初始转运动力学及其平台期摄取。INH浓度从2 × 10 ~（-6）M到10 ~（-2）M时，初始摄取速率与INH浓度呈线性关系。它被修改既不通过添加质子载体，废除脯氨酸运输，也不以下ATP耗竭砷酸盐，抑制甘油摄取，两个运输过程作为控制远二次主动运输和促进扩散，分别。微需氧或低温（4摄氏度）对初始吸收没有影响。因此，可能是INH在M.结核病通过被动扩散机制进行，并且过氧化氢酶-过氧化物酶（KatG）不参与实际运输。然而，抑制KatG活性的条件（高INH浓度、微需氧、低温）在摄取平台降低细胞放射性。有人提出，INH的运输发生被动扩散。KatG仅参与INH的氧化衍生物的细胞内积累，特别是异烟酸，其以其电离形式被捕获在细胞内。该模型解释了在存在[C-14]INH的情况下观察到的和先前已知的各种分枝杆菌种属和菌株的放射性蓄积特征。
Initial transport kinetics of isoniazid (INH) and its uptake at the plateau were studied in Mycobacterium tuberculosis H37Rv under various experimental conditions. The initial uptake velocity increased linearly with INH concentration from 2 x 10(-6) M to 10(-2) M. It was modified neither by addition of a protonophore that abolished proline transport, nor following ATP depletion by arsenate, which inhibited glycerol uptake, two transport processes taken as controls far secondary active transport and facilitated diffusion, respectively. Microaerobiosis or low temperature (4 degrees C) were without effect on initial uptake. It is thus likely that INH transport in M. tuberculosis proceeds by a passive diffusion mechanism, and that catalase-peroxidase (KatG) is not involved in the actual transport. However, conditions inhibiting KatG activity (high INH concentration, microaerobiosis, low temperature) decrease cell radioactivity at the uptake plateau. It is proposed that INH transport occurs by passive diffusion. KatG is involved only in the intracellular accumulation of oxidized derivatives of INH, especially of isonicotinic acid, which is trapped inside cells in its ionized form. This model explains observed and previously known characteristics of the accumulation of radioactivity in the presence of [C-14]INH for various species and strains of mycobacteria.