Tuberculosis is the most deadly infectious disease caused by a single infectious bacterial species, Mycobacterium tuberculosis . Between 2 to 3 million people die from this disease every year and the total number of infected individuals is estimated to be 1.7 billion around the world. M. leprae causes leprosy, with about 12 million patients world wide. Two mechanisms, the mycobacterial cell wall permeability barrier and the multidrug efflux pumps are thought to contribute to the natural drug resistance of mycobacteria. We are studying these two mechanisms using a combination of genetic, biochemical and biophysical methods.
Several projects involve investigating the biosynthetic pathway of cell wall components.
These include isolating cell wall-defective mutants, biochemically characterizing these mutants, and molecular cloning. We have recently isolated the first mutant of mycobacteria that is defective in the biosynthesis of mycolic acids, the most important constituent of the cell wall. The functional and genetic characterizations of this mutant are now underway. Dozens of new mutants have been isolated and are under studies. We are also studying efflux-mediated drug resistance in mycobacteria.