Dual targeting of DNA gyrase and topoisomerase IV:: Target interactions of heteroaryl isothiazolones in Staphylococcus aureus
Dual targeting of DNA gyrase and topoisomerase IV:: Target interactions of heteroaryl isothiazolones in Staphylococcus aureus
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DOI：
10.1128/aac.00158-07
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发表时间：
2007-07-01
影响因子：
4.9
通讯作者：
Pucci, Michael J.
中科院分区：
文献类型：
--
作者：
Cheng, Jijun;Thanassi, Jane A.;Pucci, Michael J.
杂芳基异噻唑酮类化合物(HITZ)是一类体外抗金黄色葡萄球菌活性较好的抗菌剂。我们最近发现了一系列化合物，它们对耐甲氧西林金黄色葡萄球菌(MRSA)具有很强的杀菌活性。我们报告了体外耐药性研究的结果，揭示了潜在的潜在作用机制。HITZ只在野生型金黄色葡萄球菌的第一步突变中选择gyrA突变，这表明与大多数喹诺酮类药物不同的是，DNA旋转酶是主要的靶标。这些化合物在接近MIC的浓度下表现出较低的突变频率(10(-9)至10(-10))，并保持较低的MIC(
Heteroaryl isothiazolones (HITZs) are antibacterial agents that display excellent in vitro activity against Staphylococcus aureus. We recently identified a series of these compounds that show potent bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA). We report here the results of in vitro resistance studies that reveal potential underlying mechanisms of action. HITZs selected gyrA mutations exclusively in first-step mutants of wild-type S. aureus, indicating that in contrast to the case with most quinolones, DNA gyrase is the primary target. The compounds displayed low mutation frequencies (10(-9) to 10(-10)) at concentrations close to the MICs and maintained low MICs (