Hoffmann Christian, Leis Andrew, Niederweis Michael, Plitzko Jürgen M, Engelhardt Harald
Max-Planck-Institut für Biochemie, Abteilung Molekulare Strukturbiologie, D-82152 Martinsried, Germany.
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3963-7. doi: 10.1073/pnas.0709530105. Epub 2008 Mar 3.
The cell walls of mycobacteria form an exceptional permeability barrier, and they are essential for virulence. They contain extractable lipids and long-chain mycolic acids that are covalently linked to peptidoglycan via an arabinogalactan network. The lipids were thought to form an asymmetrical bilayer of considerable thickness, but this could never be proven directly by microscopy or other means. Cryo-electron tomography of unperturbed or detergent-treated cells of Mycobacterium smegmatis embedded in vitreous ice now reveals the native organization of the cell envelope and its delineation into several distinct layers. The 3D data and the investigation of ultrathin frozen-hydrated cryosections of M. smegmatis, Myobacterium bovis bacillus Calmette-Guérin, and Corynebacterium glutamicum identified the outermost layer as a morphologically symmetrical lipid bilayer. The structure of the mycobacterial outer membrane necessitates considerable revision of the current view of its architecture. Conceivable models are proposed and discussed. These results are crucial for the investigation and understanding of transport processes across the mycobacterial cell wall, and they are of particular medical relevance in the case of pathogenic mycobacteria.
分枝杆菌的细胞壁形成了一道特殊的渗透屏障,且对其毒力至关重要。细胞壁含有可提取的脂质和长链分枝菌酸,这些物质通过阿拉伯半乳聚糖网络与肽聚糖共价连接。人们曾认为这些脂质会形成一个相当厚的不对称双层结构,但这一点从未通过显微镜或其他方法得到直接证实。现在,对包埋在玻璃态冰中的耻垢分枝杆菌未受干扰或经去污剂处理的细胞进行冷冻电子断层扫描,揭示了细胞包膜的天然组织结构及其划分为几个不同层次的情况。对耻垢分枝杆菌、卡介苗和谷氨酸棒状杆菌的超薄冷冻水合冷冻切片的三维数据及研究,确定最外层为形态对称的脂质双层。分枝杆菌外膜的结构需要对目前关于其结构的观点进行重大修正。文中提出并讨论了一些可设想的模型。这些结果对于研究和理解跨分枝杆菌细胞壁的转运过程至关重要,并且在致病性分枝杆菌的情况下具有特别的医学意义。