Brennan P J, Nikaido H
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
Annu Rev Biochem. 1995;64:29-63. doi: 10.1146/annurev.bi.64.070195.000333.
Mycobacteria, members of which cause tuberculosis and leprosy, produce cell walls of unusually low permeability, which contribute to their resistance to therapeutic agents. Their cell walls contain large amounts of C60-C90 fatty acids, mycolic acids, that are covalently linked to arabinogalactan. Recent studies clarified the unusual structures of arabinogalactan as well as of extractable cell wall lipids, such as trehalose-based lipooligosaccharides, phenolic glycolipids, and glycopeptidolipids. Most of the hydrocarbon chains of these lipids assemble to produce an asymmetric bilayer of exceptional thickness. Structural considerations suggest that the fluidity is exceptionally low in the innermost part of bilayer, gradually increasing toward the outer surface. Differences in mycolic acid structure may affect the fluidity and permeability of the bilayer, and may explain the different sensitivity levels of various mycobacterial species to lipophilic inhibitors. Hydrophilic nutrients and inhibitors, in contrast, traverse the cell wall presumably through channels of recently discovered porins.
分枝杆菌的某些成员可引发肺结核和麻风病,它们产生的细胞壁通透性异常低,这有助于它们对治疗药物产生抗性。其细胞壁含有大量C60 - C90脂肪酸,即分枝菌酸,这些分枝菌酸与阿拉伯半乳聚糖共价相连。最近的研究阐明了阿拉伯半乳聚糖以及可提取的细胞壁脂质(如基于海藻糖的脂寡糖、酚糖脂和糖肽脂)的异常结构。这些脂质的大多数烃链聚集在一起,形成了一个厚度异常的不对称双层结构。结构上的考量表明,双层结构最内层的流动性异常低,朝着外表面逐渐增加。分枝菌酸结构的差异可能会影响双层结构的流动性和通透性,并可能解释不同分枝杆菌物种对亲脂性抑制剂的不同敏感程度。相比之下,亲水性营养物质和抑制剂可能是通过最近发现的孔蛋白通道穿过细胞壁的。