Romero, I. C., Mehaffy, C., Burchmore, R. J. , Dobos-Elder, K., Brennan, P. and Walker, J. (2010) Identification of promoter-binding proteins of the fbp A and C genes in Mycobacterium tuberculosis. Tuberculosis, 90(1), pp. 25-30. (doi: 10.1016/j.tube.2009.10.001)
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Publisher's URL: http://dx.doi.org/10.1016/j.tube.2009.10.001
Abstract
The antigen 85 (Ag85) complex of Mycobacterium tuberculosis represents a promising candidate as a novel drug target and pathogenesis factor. Ag85 comprises three proteins Ag85A, B and C, (encoded by the genes fbpA, B, and C), which participate in cell wall biosynthesis, and interact with the host macrophage as fibronectin-binding proteins (fbps). Ag85 is also involved in the response to isoniazid (INH) treatment. The objective of this study was to identify potential fbp gene activators involved in the over-expression of fbp genes in response to INH. The biotinylated upstream promoter regions of fbpA and fbpC were used together with streptavidin-coated magnetic beads in DNA-binding assays, to isolate proteins with high-binding affinities from cytosolic extracts of INH-treated M. tuberculosis. Resolution of the DNA-binding proteins by 1D SDS-PAGE revealed 6 proteins with high-affinity for the fbpA promoter, and 7 with specificity the fbpC promoter. Mass spectrometric analyses [LC-ES(MS/MS)] identified proteins associated with drug resistance and stress/treatment responses, intermediary metabolism and cellular division, hypothetical proteins including a member of the MarR family of bacterial transcriptional regulators. The DNA-binding MarR protein shows potential as an authentic activator of fbp genes and functional validation of this factor is warranted.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Burchmore, Dr Richard |
| Authors: | Romero, I. C., Mehaffy, C., Burchmore, R. J., Dobos-Elder, K., Brennan, P., and Walker, J. |
| Subjects: | Q Science > Q Science (General) |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Tuberculosis |
| Publisher: | Elsevier |
| ISSN: | 1472-9792 |
| ISSN (Online): | 1873-281X |
| Published Online: | 03 December 2009 |
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