Virulence genes associated with invasion of the blood-brain barrier by M. Tuberculosis
Tuberculosis of the central nervous system (CNS) is a serious, often fatal disease primarily affecting young children. It is believed to develop after hematogenous dissemination and subsequent invasion of the CNS by Mycobacterium tuberculosis. We have developed a screen for identifying M. tuberculosis genes involved in CNS tuberculosis pathogenesis. One series of genes identified was the Rv0986-0988 operon of M. tuberculosis. This operon is believed to be involved in attachment to, invasion of, and traversal across human brain endothelial cells by M. tuberculosis. I am studying the operon through a number of means: examining the localization of proteins encoded by the operon, assigning a biochemical function to the encoded proteins, and observing the phenotype of disruption mutants of the operon in multiple models. Evaluation of these genes and identification of further genes will help in understanding the microbial and host processes involved in CNS tuberculosis.