Lab Research Focus
My laboratory is working on host parasite relationships using two different mouse models: typhoid fever and tuberculosis. Both of these organisms cause intracellular infections in their hosts meaning that they survive and cause disease while in macrophages. We are using molecular techniques to find and characterize genes in Salmonella typhimurium and Mycobacterium tuberculosis which are required for the bacteria to kill mice. We have recently cloned and characterized a regulatory gene, mviA (mouse virulence A), from Salmonella which is required for the bacteria to grow in susceptible mice. mviA is a member of the very widely distributed family of two component response regulator proteins. This type of regulation has only been known since 1986 and it is predicted that there are about 50 different regulators in most bacteria. We have found that mviA regulates the production of rpoS a sigma factor necessary for expression of genes important for surviving starvation condition. Thus mviA is a regulatory gene regulating a regulatory gene.
The outcome of an infection with S. typhimurium is determined by single amino acid changes within either the bacterial gene mviA or the host gene Ity. Ity is a gene which has been mapped and cloned from mice which regulates growth and thus virulence of a diverse group of organisms consisting of Salmonella, Mycobacterium bovis, M. lepraemurium and Leishmania donovani. We have found that mviA also regulates in vitro growth of S. typhimurium and have identified one protein whose expression is regulated by mviA that is important for virulence in mice. The aviruient Salmonella strains are effective as live vaccines. We are now beginning to screen the Mycobacterium tuberculosis genome to find the mviA counterpart and determine if mutations in it will cause avirulence which could be used to produce a better live vaccine for tuberculosis.
A second project in our laboratory involves using RFLP analysis of all isolates of M. tuberculosis from the states of Alabama and Maryland to look at the epidemiology of this pathogen. The goal of this work is to direct public health efforts to better control tuberculosis. We have found a high incidence of a few strains in the Birmingham homeless population. We are also detecting and altering treatment of patients whose cultures were contaminated in the clinical laboratory.
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