Nitric oxide generated from isoniazid activation by KatG:: Source of nitric oxide and activity against Mycobacterium tuberculosis
Nitric oxide generated from isoniazid activation by KatG:: Source of nitric oxide and activity against Mycobacterium tuberculosis
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DOI：
10.1128/aac.48.8.3006-3009.2004
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发表时间：
2004-08-01
影响因子：
4.9
通讯作者：
Deretic, V
中科院分区：
文献类型：
--
作者：
Timmins, GS;Master, S;Deretic, V
异烟酸酰肼（INH）是一种一线抗结核药物。一旦被结核分枝杆菌吸收，INH需要通过过氧化氢酶-过氧化物酶KatG活化，将INH从其前药形式转化为一系列杀菌活性物质。在这里，我们使用N-15标记的INH结合电子顺磁共振自旋捕获技术来证明一氧化氮（NO）。是由M活化INH过程中酰肼氮的氧化产生的。结核病我们还观察到一种特异性的NO清除剂在细菌培养中提供了对抗INH抗分枝杆菌活性的保护。没有检测到分枝杆菌蛋白质硝化的显著增加，这表明NO，而不是过氧亚硝酸盐，NO的硝化代谢物，与抗分枝杆菌作用有关。总之，INH衍生的NO具有生物活性，这直接有助于INK的抗分枝杆菌作用。
Isonicotinic acid hydrazide (INH) is a frontline antituberculosis agent. Once taken up by Mycobacterium tuberculosis, INH requires activation by the catalase-peroxidase KatG, converting INH from its prodrug form into a range of bactericidal reactive species. Here we used N-15-labeled INH together with electron paramagnetic resonance spin trapping techniques to demonstrate that nitric oxide (NO.) is generated from oxidation at the hydrazide nitrogens during the activation of INH by M. tuberculosis KatG. We also observed that a specific scavenger of NO. provided protection against the anti mycobacterial activity of INH in bacterial culture. No significant increases in mycobacterial protein nitration were detected, suggesting that NO. and not peroxynitrite, a nitrating metabolite of NO., is involved in antimycobacterial action. In conclusion, INH-derived NO. has biological activity, which directly contributes to the antimycobacterial action of INK.