Liberation of soluble proteins from live and dead mycobacterial cells and the implications for pathogenicity of tubercle bacilli hypothesis.
Soluble proteins liberated from live M. tuberculosis are translocated through the cytoplasmic membrane to a 'periplasmic space'. For further export of proteins across the outer permeability barrier, it is necessary to postulate an excretion mechanism possibly involving some kind of porin. Observations of the repertoire of proteins in culture filtrates after liquid culture of M. tuberculosis show that a large repertoire of various kinds of proteins cross the outer permeability barrier of tubercle bacilli indicating that the excretion mechanism has a wide range of specificities for proteins. Culture filtrates of tubercle bacilli almost always contain both truly secreted proteins and cytoplasmatically-derived proteins. It is questionable whether cytoplasmic proteins can cross an intact cytoplasmic membrane. The simplest explanation for the appearance of cytoplasmic proteins in culture filtrates of tubercle bacilli would be that they are released after disintegration of the cytoplasmic membrane in dying or dead bacilli. Tubercle bacilli armed with secreted factors that may specifically inhibit innate and adaptive immune responses, excrete these from the periplasmic space of live bacilli. Unspecific in its character, the excretion mechanism also liberates proteins that are essential for building and maintaining the cell wall, thereby reducing the effectiveness of this process. This may be part of the explanation why M. tuberculosis and other pathogenic mycobacteria grow so slowly. Finally, it may be postulated that dormant or latent tubercle bacilli use their repertoire of secreted proteins to control their intracellular habitat and that bacterial cytoplasmic proteins would not be liberated from such bacilli. The consequence would be that only immune responses to secreted proteins would be effective for elimination of the dormant stage of infection. In a situation with active infection there will be considerable growth and turnover of bacilli with liberation of all kinds of immunogenic substances from the bacilli. In this situation immunity against cytoplasmic proteins would also be effective and immunity to cytoplasmic proteins should also be effective for control of the reactivation of latent disease because as soon as the bacilli start to grow there will also be a subpopulation of dead bacilli on the arena.
Wiker
H G
HG
National Institute of Public Health, Department of Environmental Medicine, P.O. Box 4404, Nydalen, N-0403 Oslo, Norway.
D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D012995:Solubility; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
D001426:Bacterial Proteins