The outer parts of the mycobacterial envelope as permeability barriers

The permeability of mycobacteria to substances in their environment is controlled by the properties of their envelopes. Two special features are important: an outer lipid barrier based on a monolayer of characteristic mycolic acids and a capsule-like coat of polysaccharide and protein. The mycolate layer prevents entry of small hydrophilic molecules, which obtain access to the cell by way of pore-forming proteins resembling porins of Gram-negative bacteria. More lipophilic molecules can diffuse through the lipid layer. The capsule probably impedes access by macromolecules; in intracellular pathogenic species it forms the electron-transparent zone that separates the bacterium from the membrane of the host phagosome. The structure of the outer lipid barrier seems common to all mycobacteria, fast- and slow-growing, but the capsule is more abundant in slow-growing species, a group which includes all the important mycobacterial pathogens. Mycobacteria secrete proteins into their environment, which are likely to be important in the pathogenesis of mycobacterial diseases. Knowledge of how these proteins, and the polysaccharides of the capsule, cross the outer lipid barrier is minimal at present. It is likely that proper knowledge of mycobacterial permeability will enable new approaches to treatment of mycobacterial disease.