Send to

Choose Destination
J Proteome Res. 2008 Mar;7(3):855-65. doi: 10.1021/pr0703066. Epub 2008 Feb 15.

The proteomic response of Mycobacterium smegmatis to anti-tuberculosis drugs suggests targeted pathways.

Author information

Center for Systems and Synthetic Biology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.


Mycobacterium smegmatis is a fast-growing model mycobacterial system that shares many features with the pathogenic Mycobacterium tuberculosis while allowing practical proteomics analysis. With the use of shotgun-style mass spectrometry, we provide a large-scale analysis of the M. smegmatis proteomic response to the anti-tuberculosis (TB) drugs isoniazid, ethambutol, and 5-chloropyrazinamide and elucidate the drugs' systematic effects on mycobacterial proteins. A total of 2550 proteins were identified with approximately 5% false-positive identification rate across 60 experiments, representing approximately 40% of the M. smegmatis proteome ( approximately 6500 proteins). Protein differential expression levels were estimated from the shotgun proteomics data, and 485 proteins showing altered expression levels in response to drugs were identified at a 99% confidence level. Proteomic comparison of anti-TB drug responses shows that translation, cell cycle control, and energy production are down-regulated in all three drug treatments. In contrast, systems related to the drugs' targets, such as lipid, amino acid, and nucleotide metabolism, show specific protein expression changes associated with a particular drug treatment. We identify proteins involved in target pathways for the three drugs and infer putative targets for 5-chloropyrazinamide.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center