Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/1/2008
Publication Date: 6/1/2008
Citation: Abomoelak, B., Chi, J., Bannantine, J.P., Talaat, A.M. 2008. Gene Regulatory Networks Activated during Chronic Tuberculosis [abstract]. American Society for Microbiology 108th General Meeting. Poster No. U-056. Interpretive Summary:
Technical Abstract: Chronic tuberculosis represents a burden for most of world’s population. Several genes were found to be up-regulated at the late stage of chronic tuberculosis when DNA microarray protocol was used to analyze murine tuberculosis. Rv0348 is a potential transcriptional regulator that is highly expressed in the chronic stage of tuberculosis. This gene is a member of an operon of three genes with unknown function (Rv0347-Rv0349). Antibodies raised against the recombinant Rv0348 protein showed that this protein is absent from total lysates of Mycobacterium bovis BCG. When we expressed the whole operon or the Rv0348 protein alone in M.smegmatis under the control of the constitutive promoter hsp60, we were able to detect the protein by Western blot, indicating that the expression of Rv0348 is under tight regulation. To identify genes under control of this novel transcriptional regulator, we generated Rv0348 knockout mutant in M. tuberculosis by homologous recombination. The microarrays data analysis showed that several operons were up- and down- regulated in the mutant compared to M. tuberculosis H37RV such as mce1 operon (Rv0166-Rv0178). We infected BALB/c mice with the mutant and complemented strains to investigate the role of this gene in the virulence of M. tuberculosis. Identifying genes under the control of Rv0348 could represent a significant step to better understand gene networks activated during chronic tuberculosis.