Altered Protein Expression Patterns of Mycobacterium tuberculosis Induced by ATB107

Hongbo Shen; Enzhuo Yang; Feifei Wang; Ruiliang Jin; Shengfeng Xu; Qiang Huang; Honghai Wang

doi:10.1007/s12275-010-9315-6

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Research Support, Non-U.S. Gov't
Altered Protein Expression Patterns of Mycobacterium tuberculosis Induced by ATB107: Hongbo Shen ¹, Enzhuo Yang ¹, Feifei Wang ¹, Ruiliang Jin ², Shengfeng Xu ¹, Qiang Huang ¹, Honghai Wang ¹; Journal of Microbiology 2010;48(3):337-346.
DOI: https://doi.org/10.1007/s12275-010-9315-6
Published online: June 23, 2010

¹State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China, ²Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, P. R. China

Corresponding author: Qiang Huang , Tel: +86-21-6564-3777,
Honghai Wang , Tel: +86-21-6564-3777,

Received: 12 October 2009 • Accepted: 15 March 2010

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Abstract

ATB107 is a potent inhibitor of indole-3-glycerol phosphate synthase (IGPS). It can effectively inhibit the growth of clinical isolates of drug-resistant Mycobacterium tuberculosis strains as well as M. tuberculosis H37Rv. To investigate the mechanism of ATB107 action in M. tuberculosis, two-dimensional gel electrophoresis coupled with MALDI-TOF-MS analysis (2-DE-MS) was performed to illustrate alterations in the protein expression profile in response to ATB107. Results show that ATB107 affected tryptophan biosynthesis by decreasing the expression of protein encoded by Rv3246c, the transcriptional regulatory protein of MtrA belonging to the MtrA-MtrB two-component regulatory system, in both drug-sensitive and drug-resistant virulent strains. ATB107 might present a stress condition similar to isoniazid (INH) or ethionamide for M. tuberculosis since the altered expression in response to ATB107 of some genes, such as Rv3140, Rv2243, and Rv2428, is consistent with INH or ethionamide treatment. After incubation with ATB107, the expression of 2 proteins encoded by Rv0685 and Rv2624c was down-regulated while that of protein encoded by Rv3140 was up-regulated in all M. tuberculosis strains used in this study. This may be the common response to tryptophan absence; however, relations to ATB107 are unknown and further evaluation is warranted.

Keywords: M. tuberculosis;ATB107;indole-3-glycerol phosphate synthase;inhibitor;tryptophan biosynthesis

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Altered Protein Expression Patterns of Mycobacterium tuberculosis Induced by ATB107

J. Microbiol. 2010;48(3):337-346. Published online June 23, 2010

DOI: https://doi.org/10.1007/s12275-010-9315-6

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