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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

1
Center for Systems and Synthetic Biology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.

Abstract

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.

PMID:
18275136
DOI:
10.1021/pr0703066
[Indexed for MEDLINE]

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