Progress for deciphering Mycobacterium tuberculosis pathogenicity

Tuberculosis remains the greatest cause of death worldwide due to a single prokaryotic pathogen. Despite its importance, the basis of pathogenicity remains poorly understood. However, tools for molecular genetic analysis, such as gene fusions, counter-selectable markers, allelic exchange and transposon mutagenesis have been recently constructed, moreover, the genome sequence has been completed, which will probably help the development of new strategies for preventive and therapeutic treatments. Surprisingly, genome analysis has not revealed classical virulence factors such as toxins or classical invasions. Using a reporter system for exported sequence, Erp (Exported Repeated Protein) has been characterized, and it has been recently shown that this surface protein is a key factor for virulence, in the sense that erp is indispensable for persistence and multiplication both in vitro and in vivo in the mouse model. This is the first report of a non-auxotrophic mutation leading to attenuation in Mycobacterium tuberculosis. Using a combination of biochemical and cell biology techniques, we are currently investigating the role of the Erp protein in the pathogenic properties of the tubercle bacillus.