Despite existing medicines and BCG vaccination, tuberculosis continues to kill people. The incidence of the illness is increasing in both developing and industrialised countries. During the next ten years, ninety million adults will be affected by the disease. The emergence of strains resistant to antibiotics and the association of M. tuberculosis with HIV have made the increasing incidence of this illness a major public health problem.
Tuberculosis is caused by the members of a family of mycobacteria: Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium africanum. The virulence or pathogenicity of these agents depends on their ability to multiply in their host.
At the Institut Pasteur, the Mycobacterial Genetics Unit, headed by Brigitte GICQUEL, is trying to identify the virulence factors of the bacteria responsible for tuberculosis. If we can inactivate these genes, we should be able to develop new live attenuated vaccines. BCG vaccination reduces the number of new cases and prevents serious forms of the illness in young children, but the immunity conferred by this vaccine gradually decreases over ten years or so. The development of new vaccines is therefore of particular importance.
The first tuberculosis virulence gene has just been identified in M. tuberculosis. The gene is called erp and it encodes a surface protein that is required for the multiplication of the bacterium in host cells. Brigitte Gicquel's team used mutagenesis techniques to develop "mutant" strains of M. tuberculosis and of the vaccine strain, M. bovis BCG, in which erp is inactivated. They showed that the inactivation of erp prevents the production of the surface protein encoded by the gene and considerably reduces the multiplication of M. tuberculosis and M. bovis in cultured macrophages and mice. The reintroduction of erp into the mutant strains restored their capacity to multiply.
Thus, this work suggests that the erp gene could be used to attenuate the virulence of M. tuberculosis, enabling new live attenuated vaccines against tuberculosis to be developed.