Tuberculosis exacts an enormous burden in morbidity and mortality on the global population. With the advent of the HIV epidemic and multiple drug resistances, disease due to tuberculosis has increased leading to a need for research into the basic mechanisms of pathogenesis. The long-range goal of this proposal is to understand how Mycobacterium tuberculosis, the causative agent of tuberculosis, can sense environmental stresses, up regulate critical genes, and survive in the hostile environment of the host. When M. tuberculosis invades a host it infects human macrophages. M. tuberculosis can also be found within host granulomas that have been shown to have an acidic pH. The putative promoter regions of the M. tuberculosis genes lipF and Rv0834c have been identified to be upregulated in response to acidic pH.
The specific aims of this proposal are to: 1) characterize the putative promoter regions of lipF and Rv0834c to better understand how acid induced promoters are regulated 2) determine if lipF and Rv0834c are required for mycobacteria to resist acidic stress and identify additional stresses which may upregulate these genes. The expectation is that this work will result in the characterization of acid responsive promoter regions and provide the groundwork for the eventual identification of a general mechanism by which M. tuberculosis can resist environmental stresses such as acidic stress. This work is significant because it will contribute to a greater understanding of mycobacterial stress response and ultimately survival and persistence in the host during infection.
| Richter, Laetitia; Saviola, Beatrice (2009) The lipF promoter of Mycobacterium tuberculosis is upregulated specifically by acidic pH but not by other stress conditions. Microbiol Res 164:228-32 |
| Saviola, Beatrice (2009) Phage L5 integrating vectors are present within the Mycobacterial Cell in an equilibrium between integrated and excised states. Cancer Ther 7:35-42 |
| Richter, Laetitia; Tai, Wendy; Felton, Jeffrey et al. (2007) Determination of the minimal acid-inducible promoter region of the lipF gene from Mycobacterium tuberculosis. Gene 395:22-8 |
| Saviola, Beatrice; Bishai, William R (2004) Method to integrate multiple plasmids into the mycobacterial chromosome. Nucleic Acids Res 32:e11 |
