Chorismate Mutase - Chorismate Mutase and Tuberculosis

Chorismate Mutase and Tuberculosis

Tuberculosis is a terrible disease that accounts for more deaths than any other single infection around the world. The fact that chorismate mutase is found only in fungi, bacteria and higher plants makes it an easy target for the creation of anti-bacterials as well as herbicides. In addition, the low sequence homology between known chorismate mutase provides the opportunity to develop unique inhibitors. This has been the case in the fight against antibiotic-resistant Tuberculosis (TB). The CM found in Myobacterium tuberculosis is vital to its overall survival and subsequent pathogenicity. Humans do not contain CM, so it is being used as a target to develop an antibiotic to fight the disease. M. tuberculosis contains two genes, Rv1885c and Rv0948c, that code for its chorismate mutase. These CM are secreted out of the cell to provide support for M. tuberculosis when it is in an aromatic amino acid deficient medium.

It has also been proposed that the CM could interact with host macrophages and might be importance in virulence. This idea is supported by evidence that the AroQ CM of other pathogenic bacteria, such as Salmonella typhi have been shown to be involved in virulence. There is one gene in particular, Rv1885c, that is the major contributor to CM activity that has become the focus of study. Rohini Qamra et al. have solved a crystal structure of the CM of Myobacterium tuberculosis (MtbCM) and propose that a proline-rich portion of the protein is responsible for binding to the host cell macrophage's cell surface receptors.