Mycobacterium tuberculosis has infected about 2 billion people and causes the death of about two million people every year, more than any other single infectious agent. The mycobacterial outer membrane is an extremely efficient permeability barrier that is considered as the major determinant of the intrinsic resistance of mycobacteria to most antibiotics. This restricts the armamentory for tuberculosis (TB) chemotherapy to a handful of drugs.
Porins are water-filled channel proteins in the outer membrane of mycobacteria and provide the major pathway for influx of hydrophilic compounds. Our ultimate goal is to examine the structure and function of mycobacterial porins and to exploit this knowledge for the design of new TB drugs that efficiently overcome the outer membrane permeability barrier.
Repression of porin gene expression plays a major role in protecting M. tuberculosis from toxic compounds in macrophages and likely contributes to the persistence of M. tuberculosis inside the human body. Therefore, we want to understand how expression of porin genes is regulated. Interference with this regulatory mechanism is likely to open a new path in TB chemotherapy by potentiating the efficacy of known drugs against M. tuberculosis.
