Bausch & Lomb, Inc., Rochester, N.Y., USA.
Chemotherapy. 2011;57(5):363-71. doi: 10.1159/000330858. Epub 2011 Oct 12.
The impact of mutations in DNA gyrase and topoisomerase IV on minimum inhibitory concentrations (MICs) was investigated to better understand why besifloxacin has a higher potency against Staphylococcus aureus when compared to other fluoroquinolones, which was especially pronounced against ciprofloxacin-resistant isolates.
MICs were determined for 52 clinical isolates against besifloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. The genes encoding GyrA, GyrB, ParC, and ParE were sequenced and the potential impact of mutations assessed in light of recent structural data.
For all fluoroquinolones tested, the MICs increased with the number of mutations in the quinolone resistance-determining regions. However, this increase was the smallest for besifloxacin and the largest for ciprofloxacin and levofloxacin. In addition to the commonly observed mutations in ParC and GyrA, more unusual mutations in ParE, such as Asp-432→His or Pro-585→Ser, were also detected.
Compared to earlier fluoroquinolones, the higher potency of besifloxacin suggests that the drug's unique combination of a 7-azepinyl ring and an 8-chloro-substituent results in unique interactions with DNA gyrase and topoisomerase IV.
本研究旨在探讨 DNA 回旋酶和拓扑异构酶 IV 突变对最小抑菌浓度（MIC）的影响，以更好地理解与其他氟喹诺酮类药物相比，贝西沙星对金黄色葡萄球菌具有更高抗菌活性的原因，尤其是对耐环丙沙星的分离株。
测定了 52 株临床分离株对贝西沙星、莫西沙星、加替沙星、环丙沙星和左氧氟沙星的 MIC。测序了编码 GyrA、GyrB、ParC 和 ParE 的基因，并根据最新的结构数据评估了突变的潜在影响。
对于所有测试的氟喹诺酮类药物，喹诺酮耐药决定区突变的数量越多，MIC 值就越高。然而，贝西沙星的 MIC 值增加最小，而环丙沙星和左氧氟沙星的 MIC 值增加最大。除了 ParC 和 GyrA 中常见的突变外，还检测到 ParE 中一些不常见的突变，如 Asp-432→His 或 Pro-585→Ser。
与早期的氟喹诺酮类药物相比，贝西沙星的高抗菌活性表明，该药物独特的 7-氮杂环庚烷环和 8-氯取代基的组合与 DNA 回旋酶和拓扑异构酶 IV 产生了独特的相互作用。
