A secondary mode of action of polymyxins against Gram-negative bacteria involves the inhibition of NADH-quinone oxidoreductase activity.

A secondary mode of action of polymyxins against Gram-negative bacteria involves the inhibition of NADH-quinone oxidoreductase activity.
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DOI:
10.1038/ja.2013.111
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发表时间:
2014-02
期刊:
The Journal of antibiotics
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检测了多粘菌素B和黏菌素对三种革兰氏阴性菌的II型NADH-醌氧化还原酶(NDH-2)的抑制能力。多粘菌素B和黏菌素以浓度依赖性方式抑制所有分离株制剂中的NDH-2活性。用大肠杆菌对多粘菌素B抑制NDH-2的机制进行了详细的研究。大肠杆菌内膜制备物,并符合混合抑制模型,相对于泛醌-1和非竞争性抑制模型相对于NADH。这表明抑制细菌内膜中的重要呼吸酶是多粘菌素的次要作用模式之一。
Polymyxin B and colistin were examined for their ability to inhibit the type II NADH-quinone oxidoreductases (NDH-2) of three species of Gram-negative bacteria. Polymyxin B and colistin inhibited the NDH-2 activity in preparations from all of the isolates in a concentration-dependent manner. The mechanism of NDH-2 inhibition by polymyxin B was investigated in detail with E. coli inner membrane preparations and conformed to a mixed inhibition model with respect to ubiquinone-1 and a non-competitive inhibition model with respect to NADH. These suggest inhibition of vital respiratory enzymes in the bacterial inner membrane represents one of the secondary modes of action for polymyxins.
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