Braga P C, Ricci D, Dal Sasso M
Department of Pharmacology, School of Medicine, University of Milan, Italy.
J Chemother. 2002 Aug;14(4):336-41. doi: 10.1179/joc.2002.14.4.336.
Daptomycin is a novel, rapidly bactericidal in vitro antibiotic that is under investigation for the treatment of serious Gram-positive infections. Although daptomycin appears to disrupt membrane function, the precise mechanism of action has not been fully elucidated. Atomic force microscopy (AFM) is an innovative technique that allows high-resolution visualization and digital image manipulation of cell surface structures in 3 dimensions without the use of photons and electrons. The aim of this study was to use AFM to investigate the morphostructural changes in Bacillus cereus that occur upon daptomycin administration. The effects of daptomycin at 4x and 8x the minimal inhibitory concentration were visualized during an 8-hour incubation period. Atomic force microscopy images showed aberrant bacterial surface formations, including flattening and shrinking of cells and leakage of cytoplasm through the membrane. In addition to structural changes, the destabilization of flagella was also observed. These results support previous data suggesting that daptomycin disrupts membrane function.
达托霉素是一种新型的体外快速杀菌抗生素,目前正在进行治疗严重革兰氏阳性菌感染的研究。尽管达托霉素似乎会破坏膜功能,但其确切作用机制尚未完全阐明。原子力显微镜(AFM)是一种创新技术,可在不使用光子和电子的情况下对细胞表面结构进行三维高分辨率可视化和数字图像处理。本研究的目的是使用AFM研究蜡样芽孢杆菌在给予达托霉素后发生的形态结构变化。在8小时的孵育期内观察到达托霉素在4倍和8倍最小抑菌浓度时的作用效果。原子力显微镜图像显示细菌表面出现异常形态,包括细胞扁平化和萎缩以及细胞质通过细胞膜泄漏。除了结构变化外,还观察到鞭毛的不稳定。这些结果支持了先前的数据,表明达托霉素会破坏膜功能。