The influence of fluoroquinolone drugs on the bacterial growth of S-epidermidis utilizing the unique potential of vibrational spectroscopy
The influence of fluoroquinolone drugs on the bacterial growth of S-epidermidis utilizing the unique potential of vibrational spectroscopy
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DOI：
10.1021/jp0678397
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发表时间：
2007-04-19
影响因子：
2.9
通讯作者：
Popp, J.
中科院分区：
文献类型：
--
作者：
Neugebauer, U.;Schmid, U.;Popp, J.
许多抗生素的耐药性增加使得新药的设计成为必要。为了帮助有针对性地寻找新的结构和阐明现有药物的作用方式，需要强大的分析技术。在这项工作中，振动光谱是用来揭示更多的迄今难以捉摸的相互作用的促旋酶抑制剂的氟喹诺酮类与其生物靶标内的革兰氏阳性细菌表皮葡萄球菌通过调查全细胞的变化，发生作为一个结果的药物氟沙星的存在。记录未受干扰的细菌和不同药物浓度（0.08、0.16、0.27和0.62 μ g阿氟沙星/mL细菌培养物）的细菌的IR吸收和具有共振激发（λ（exc）= 532 nm）和与生物靶DNA和促旋酶的芳香族氨基酸共振（λ（exc）= 244 nm）的拉曼光谱。采用聚类分析、主成分分析、Fisher线性判别分析结合变量选择等统计方法，对药物作用引起的光谱变化进行分析。受药物作用影响最大的波数可以分配给蛋白质和DNA部分，支持氟喹诺酮、促旋酶和DNA的三级复合物的拟议机制。
Increasing resistance of many antibiotics has made the design of new drugs necessary. To assist a target-oriented search for new structures and for the elucidation of the mode of action of existing drugs, powerful analytical techniques are required. In this work, vibrational spectroscopy is used to shed more light on the as-yet elusive interaction of gyrase inhibitors of the fluoroquinolone type with their biological target inside the Gram-positive bacterium Staphylococcus epidermidis by investigating whole-cell changes that occur as a result of the presence of the drug moxifloxacin. IR absorption and Raman spectra with excitation off resonance (lambda(exc) = 532 nm) and in resonance with the biological targets DNA and the aromatic amino acids of gyrase (lambda(exc) = 244 nm) were recorded for unperturbed bacteria and bacteria in varying drug concentrations (0.08, 0.16, 0.27, and 0.62 mu g moxifloxacin/mL bacterial culture). The spectral changes caused by the action of the drug were analyzed with the help of statistical methods, such as hierarchical cluster analysis (HCA), principal component analysis (PCA), and Fisher's linear discriminant analysis (LDA) combined with variable selection. The wavenumbers mostly affected by the action of the drug could be assigned to protein and DNA moieties, supporting the proposed mechanisms of a tertiary complex of the fluoroquinolone, the enzyme gyrase, and DNA.