Bu, W. Palmeri, D., Krishnan, R., Marin, R., Aris, V.M., Soteropoulos, P. and Lukac, D.M. (2008) Identification of Direct Transcriptional Targets of the Kaposi’s sarcoma-associated herpesvirus (KSHV) Rta Lytic Switch Protein by conditional nuclear localization. Journal of Virology 82:10709-23
During lung infection Mycobacterium tuberculosis resides inside macrophages and subverts the bactericidal mechanisms of these professional phagocytes. Comprehension of this host-pathogen relationship is fundamental for the development of new therapies to cure and prevent tuberculosis. In this project we compared the gene expression profiling of M. tuberculosis strain H37Rv and a mutant strain with a deletion of the Sigma factor E (SigE) after infection of human macrophage-like cells (THP-1). We conversely analyzed the gene expression profiles of the THP1-1 cells and resting and IFN-gamma treated mouse bone marrow macrophages after infection with the sigE mutant or the wild type strain H37Rv. We were able to conclude that the gene expression profile of M. tuberculosis inside THP-1 cells suggests the perturbation of the cell envelope is one of the major intracellular stresses inside THP-1 macrophages, and that SigE controls the expression of Mtb factors related to maintenance of cell envelope function. We also determined that inflammatory response of both, the THP-1 cells and the mouse bone marrow macrophages was enhanced after infection with the sigE mutant strain as compared to the wild type strain. Our results demonstrate that the Mtb sigma factor E regulates the expression of bacterial components important for the maintenance of the cell envelope that helps the microorganism to cope with environmental stress and to suppress the host immune system and the antibacterial response.
Fontán, P., Aris, V., Ghanny, S., Soteropoulos, P. and Smith, I. (2008) The global transcriptional profile of Mycobacterium tuberculosis during THP-1 human macrophage infection. Infect. Immun. 76:717-25.
Fontán, P., Aris, V., Alvarez, M.E. Ghanny, S., Cheng, J., Soteropoulos, P. Trevani, A., Pine, R. and Smith, I. (2008) Mycobacterium tuberculosis SigE Regulon Modulates the Host Inflammatory Response. Journal of Infectious Diseases 198:877-85