Smith M A, Edwards D I
Chemotherapy Research Unit, University of East London, UK.
J Antimicrob Chemother. 1995 Jun;35(6):751-64. doi: 10.1093/jac/35.6.751.
Metronidazole sensitive (MtzS) and resistant (MtzR) strains of Helicobacter pylori were tested for their sensitivities to eleven nitroheterocyclic drugs of known reduction potential under a wide range of environmental conditions. Under microaerophilic conditions, MtzR strains were sensitive to all the 2-nitroimidazoles, resistant to every 5-nitroimidazole, and slightly sensitive to the nitrothiazole, niridazole. MtzS strains were sensitive to all the nitroimidazoles except for 4(5)-nitroimidazole which has the lowest redox potential of all the drugs investigated. MtzS strains displayed the greatest sensitivity towards niridazole and satranidazole, the latter having the highest redox potential of the 5-nitroimidazoles. High and low oxygen tensions had no effect on the activity of the drugs but periods of anaerobic incubation caused resistant strains to become sensitive to the 5-nitroimidazoles. Superoxide dismutase and catalase were not induced by metronidazole and enzyme levels showed no correlation with resistance patterns. The results show that futile cycling does not occur in H. pylori and that the mechanism of action of the nitroimidazoles is related to their redox potential. Anaerobiosis abolishes resistance to metronidazole which suggests that it may be mediated through the activation of anaerobic metabolic pathways which function less under microaerophilic conditions or not at all.
在广泛的环境条件下，对甲硝唑敏感（MtzS）和耐药（MtzR）的幽门螺杆菌菌株进行了测试，以检测它们对11种已知还原电位的硝基杂环药物的敏感性。在微需氧条件下，MtzR菌株对所有2-硝基咪唑敏感，对每种5-硝基咪唑耐药，对硝基噻唑硝唑尼特稍有敏感。MtzS菌株对除4(5)-硝基咪唑外的所有硝基咪唑敏感，4(5)-硝基咪唑在所研究的所有药物中具有最低的氧化还原电位。MtzS菌株对硝唑尼特和塞曲硝唑表现出最大的敏感性，后者在5-硝基咪唑中具有最高的氧化还原电位。高氧和低氧张力对药物活性没有影响，但厌氧孵育期会使耐药菌株对5-硝基咪唑敏感。甲硝唑不会诱导超氧化物歧化酶和过氧化氢酶，酶水平与耐药模式无关。结果表明，幽门螺杆菌中不会发生无效循环，硝基咪唑的作用机制与其氧化还原电位有关。厌氧状态消除了对甲硝唑的耐药性，这表明它可能是通过激活厌氧代谢途径介导的，这些途径在微需氧条件下功能较弱或根本不发挥作用。
