One of the most prominent features of M. tuberculosis is its unusual outer membrane that plays a crucial role in the intrinsic drug resistance and in survival of M. tuberculosis in vivo. This membrane is functionalized by intriguing proteins which provide essential functions such as nutrient uptake, have new structures and likely function by novel mechanisms. We discovered the first outer membrane channel protein in mycobacteria, obtained the first crystal structure of a mycobacterial outer membrane protein and demonstrated that mycobacteria indeed have two membranes. Our goal is to identify and characterize outer membrane proteins of M. tuberculosis. One of those proteins, CpnT, enables the secretion of the major exotoxin of M. tuberculosis, a NAD+ glycohydrolase which triggers necroptosis in infected macrophages. We use state-of-the art genetic, biochemical and biophysical approaches to achieve our aims.
