The capsule of Mycobacterium tuberculosis and its implications for pathogenicity.
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.
Daffé
M
M
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Toulouse, France. daffe@ipbs.fr
Etienne
G
G
D001422:Bacterial Adhesion / Q000502:physiology; D016667:Bacterial Capsules / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000472:pathogenicity*; D014376:Tuberculosis / Q000276:immunology