We study the pathogenesis of tuberculosis and are interested in both the microbial and host factors contributing to this complex infection. Mycobacterium tuberculosis, the causative organism resides within macrophages of infected hosts and elicits the formation of granulomas, organized collections of modified macrophhges and lymphocytes. In this milieu, the organism is able to persist for decades without causing disease. In a small proportion of infected individuals, the infection re-activates to cause serious disease commonly called active tuberculosis.
Tuberculosis remains the single largest infectious cause of death world-wide.
It also replicates in cultured mammalian macrophages using strategies identical to those of M. tuberculosis. M. marinum offers the advantages of a multiplicity of natural animal hosts that can be studied in the laboratory, relative safety, rapid growth, and easy amenability to genetic and cell biological approaches. A subset of these genes is also expressed in cultured macrophages. Other DFI screens could be designed to uncover additional aspects of gene regulation in disease progression, eg. We are currently studying the mechanistic basis of the role of this new class of host-induced virulence determinants using a combination of genetic, biochemical and cell biological approaches.