Altered Protein Expression Patterns of Mycobacterium Tuberculosis Induced by ATB107

Overview

Journal J Microbiol

Specialty Microbiology

Date 2010 Jun 24

PMID 20571952

Citations 5

Authors

Hongbo Shen

Enzhuo Yang

Feifei Wang

Ruiliang Jin

Shengfeng Xu

Qiang Huang

Honghai Wang

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Karakousis P, Williams E, Bishai W . Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis. J Antimicrob Chemother. 2007; 61(2):323-31. DOI: 10.1093/jac/dkm485. View

Betts J, Lukey P, Robb L, McAdam R, Duncan K . Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol. 2002; 43(3):717-31. DOI: 10.1046/j.1365-2958.2002.02779.x. View

Mawuenyega K, Forst C, Dobos K, Belisle J, Chen J, Bradbury E . Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Mol Biol Cell. 2004; 16(1):396-404. PMC: 539182. DOI: 10.1091/mbc.e04-04-0329. View

Zheng H, Lu L, Wang B, Pu S, Zhang X, Zhu G . Genetic basis of virulence attenuation revealed by comparative genomic analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv. PLoS One. 2008; 3(6):e2375. PMC: 2440308. DOI: 10.1371/journal.pone.0002375. View

Rengarajan J, Bloom B, Rubin E . Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci U S A. 2005; 102(23):8327-32. PMC: 1142121. DOI: 10.1073/pnas.0503272102. View

Lamichhane G, Zignol M, Blades N, Geiman D, Dougherty A, Grosset J . A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2003; 100(12):7213-8. PMC: 165855. DOI: 10.1073/pnas.1231432100. View

Mattow J, Siejak F, Hagens K, Becher D, Albrecht D, Krah A . Proteins unique to intraphagosomally grown Mycobacterium tuberculosis. Proteomics. 2006; 6(8):2485-94. DOI: 10.1002/pmic.200500547. View

Zahrt T, Deretic V . An essential two-component signal transduction system in Mycobacterium tuberculosis. J Bacteriol. 2000; 182(13):3832-8. PMC: 94557. DOI: 10.1128/JB.182.13.3832-3838.2000. View

Shen H, Wang F, Zhang Y, Huang Q, Xu S, Hu H . A novel inhibitor of indole-3-glycerol phosphate synthase with activity against multidrug-resistant Mycobacterium tuberculosis. FEBS J. 2008; 276(1):144-54. DOI: 10.1111/j.1742-4658.2008.06763.x. View

10.

Rosenkrands I, Slayden R, Crawford J, Aagaard C, Barry 3rd C, Andersen P . Hypoxic response of Mycobacterium tuberculosis studied by metabolic labeling and proteome analysis of cellular and extracellular proteins. J Bacteriol. 2002; 184(13):3485-91. PMC: 135148. DOI: 10.1128/JB.184.13.3485-3491.2002. View

11.

Manganelli R, Voskuil M, Schoolnik G, Smith I . The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol Microbiol. 2001; 41(2):423-37. DOI: 10.1046/j.1365-2958.2001.02525.x. View

12.

Walters S, Dubnau E, Kolesnikova I, Laval F, Daffe M, Smith I . The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol Microbiol. 2006; 60(2):312-30. DOI: 10.1111/j.1365-2958.2006.05102.x. View

13.

Jungblut P, Schaible U, Mollenkopf H, Zimny-Arndt U, Raupach B, Mattow J . Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Mol Microbiol. 1999; 33(6):1103-17. DOI: 10.1046/j.1365-2958.1999.01549.x. View

14.

Gandhi N, Moll A, Sturm A, Pawinski R, Govender T, Lalloo U . Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006; 368(9547):1575-80. DOI: 10.1016/S0140-6736(06)69573-1. View

15.

OToole R, Smeulders M, Blokpoel M, Kay E, Lougheed K, Williams H . A two-component regulator of universal stress protein expression and adaptation to oxygen starvation in Mycobacterium smegmatis. J Bacteriol. 2003; 185(5):1543-54. PMC: 148059. DOI: 10.1128/JB.185.5.1543-1554.2003. View

16.

Wilson M, Derisi J, Kristensen H, Imboden P, Rane S, Brown P . Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proc Natl Acad Sci U S A. 1999; 96(22):12833-8. PMC: 23119. DOI: 10.1073/pnas.96.22.12833. View

17.

Sassetti C, Boyd D, Rubin E . Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol. 2003; 48(1):77-84. DOI: 10.1046/j.1365-2958.2003.03425.x. View

18.

Mehra A, Lee K, Hatzimanikatis V . Insights into the relation between mRNA and protein expression patterns: I. Theoretical considerations. Biotechnol Bioeng. 2004; 84(7):822-33. DOI: 10.1002/bit.10860. View

19.

Florczyk M, McCue L, Stack R, Hauer C, McDonough K . Identification and characterization of mycobacterial proteins differentially expressed under standing and shaking culture conditions, including Rv2623 from a novel class of putative ATP-binding proteins. Infect Immun. 2001; 69(9):5777-85. PMC: 98695. DOI: 10.1128/IAI.69.9.5777-5785.2001. View

20.

Denkin S, Byrne S, Jie C, Zhang Y . Gene expression profiling analysis of Mycobacterium tuberculosis genes in response to salicylate. Arch Microbiol. 2005; 184(3):152-7. DOI: 10.1007/s00203-005-0037-9. View