Daffé M, Etienne G
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Toulouse, France.
Tuber Lung Dis. 1999;79(3):153-69. doi: 10.1054/tuld.1998.0200.
Mycobacterium tuberculosis, one of the most prevalent causes of death worldwide, is a facultative intracellular parasite that invades and persists within the macrophages. Within host cells, the bacterium is surrounded by a capsule which is electron-transparent in EM sections, outside the bacterial wall and plasma membrane. Although conventional processing of samples for microscopy studies failed to demonstrate this structure around in vitro-grown bacilli, the application of new microscopy techniques to mycobacteria allows the visualization of a thick capsule in specimen from axenic cultures of mycobacteria. Gentle mechanical treatment and detergent extraction remove the outermost components of this capsule which consist primarily of polysaccharide and protein, with small amounts of lipid. Being at the interface between the bacterium and host cells, the capsule and its constituents would be expected to be involved in bacterial pathogenicity and past work supports this concept. Recent studies have identified several capsular substances potentially involved in the key steps of pathogenicity. In this respect, some of the capsular glycans have been shown to mediate the adhesion to and the penetration of bacilli into the host's cells; of related interest, secreted and/or surface-exposed enzymes and transporters probably involved in intracellular multiplication have been characterized in short-term culture filtrates of M. tuberculosis. In addition, the presence of inducible proteases and lipases has been shown. The capsule would also represent a passive barrier by impeding the diffusion of macromolecules towards the inner parts of the envelope; furthermore, secreted enzymes potentially involved in the detoxification of reactive oxygen intermediates have been identified, notably catalase/peroxidase and superoxide dismutase, which may participate to the active resistance of the bacterium to the host's microbicidal mechanisms. Finally, toxic lipids and contact-dependent lytic substances, as well as constituents that inhibit both macrophage-priming and lymphoproliferation, have been found in the capsule, thereby explaining part of the immunopathology of tuberculosis.
结核分枝杆菌是全球最常见的致死原因之一，是一种兼性细胞内寄生虫，可侵入巨噬细胞并在其中持续存在。在宿主细胞内，该细菌被一层包膜包围，在电子显微镜切片中，该包膜在细菌细胞壁和质膜之外，呈电子透明状。尽管用于显微镜研究的传统样本处理方法未能在体外培养的杆菌周围显示出这种结构，但将新的显微镜技术应用于分枝杆菌，可使来自分枝杆菌无菌培养物的标本中可见一层厚厚的包膜。温和的机械处理和去污剂提取可去除该包膜的最外层成分，这些成分主要由多糖和蛋白质组成，还有少量脂质。由于处于细菌与宿主细胞的界面，预计包膜及其成分会参与细菌致病性，过去的研究支持了这一概念。最近的研究已经确定了几种可能参与致病性关键步骤的荚膜物质。在这方面，一些荚膜聚糖已被证明可介导杆菌与宿主细胞的粘附以及杆菌对宿主细胞的穿透；相关的是，在结核分枝杆菌的短期培养滤液中已鉴定出可能参与细胞内增殖的分泌和/或表面暴露的酶和转运蛋白。此外，已证明存在诱导型蛋白酶和脂肪酶。包膜还可能是一种被动屏障，可阻止大分子向包膜内部扩散；此外，已鉴定出可能参与活性氧中间体解毒的分泌酶，特别是过氧化氢酶/过氧化物酶和超氧化物歧化酶，它们可能参与细菌对宿主杀菌机制的主动抵抗。最后，在包膜中发现了有毒脂质和接触依赖性裂解物质，以及抑制巨噬细胞启动和淋巴细胞增殖的成分，从而解释了结核病免疫病理学的部分原因。
