The important human pathogen Mycobacterium tuberculosis does not belong to the Gram negative bacteria. Yet, if these bacteria are studied using electron microscopy, they have a similar cell envelope profile. Biochemical analysis showed that the mycobacterial cell envelope contains, in addition to a normal inner membrane, an outer membrane composed of very large and unique lipids called mycolic acids that are intercalated with other unusual (glyco)lipids. The presence of this second membrane implies that mycobacteria also must have a specialized secretion pathway. Recently, we and others have identified such a secretion pathway, which is now called type VII secretion. Interestingly, pathogenic mycobacteria have up to five different type VII secretion systems. A considerable body of work has now demonstrated that several these secretion systems are important for the mycobacterial viability and/or survival inside the host.
In our group, we study different aspects of the type VII secretion systems. The first aspect covers the working of this secretion machinery. We have identified different substrates for these secretion systems, but how are these substrates specifically recognized? In addition, we have isolated the membrane complex of type VII secretion systems and are at the moment biochemically and structurally characterizing this large complex. A different aspect is the effect of protein secretion on virulence. What is the function of the secreted proteins and how do they interact with the host? Finally, we will use the information on this secretion system to improve the current tuberculosis vaccine strain M. bovis BCG and identify new compounds that block this persistent pathogen.