The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of Metabolism
Open accessAbstract
The differential transcriptional response of Mycobacterium tuberculosis to drugs and growth-inhibitory conditions was monitored to generate a data set of 430 microarray profiles. Unbiased grouping of these profiles independently clustered agents of known mechanism of action accurately and was successful at predicting the mechanism of action of several unknown agents. These predictions were validated biochemically for two agents of previously uncategorized mechanism, pyridoacridones and phenothiazines. Analysis of this data set further revealed 150 underlying clusters of coordinately regulated genes offering the first glimpse at the full metabolic potential of this organism. A signature subset of these gene clusters was sufficient to classify all known agents as to mechanism of action. Transcriptional profiling of both crude and purified natural products can provide critical information on both mechanism and detoxification prior to purification that can be used to guide the drug discovery process. Thus, the transcriptional profile generated by a crude marine natural product recapitulated the mechanistic prediction from the pure active component. The underlying gene clusters further provide fundamental insights into the metabolic response of bacteria to drug-induced stress and provide a rational basis for the selection of critical metabolic targets for screening for new agents with improved activity against this important human pathogen.
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Cites
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Cited by
Hurdle, J. G., O'Neill, A. J., Chopra, I., & Lee, R. E. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2474 · Cited by 871
Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis
Makarov, V., Manina, G., Mikusova, K., Möllmann, U., Ryabova, O., Saint-Joanis, B., Dhar, N., Pasca, M. R., Buroni, S., Lucarelli, A. P., et al. (2009) · Science · doi:10.1126/science.1171583 · Cited by 740
The Enduring Hypoxic Response of Mycobacterium tuberculosis
Rustad, T. R., Harrell, M. I., Liao, R., & Sherman, D. R. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001502 · Cited by 491
Antituberculosis drugs: Ten years of research
Janin, Y. L. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.01.030 · Cited by 485
Tuberculosis — metabolism and respiration in the absence of growth
Boshoff, H. I. M., & Barry, C. E. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1065 · Cited by 448
Self-citation
Metadata
- Authors
- Boshoff, H. I. M., Myers, T. G., Copp, B. R., McNeil, M. R., Wilson, M. A., & Barry, C. E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 279
- Issue
- 38
- Pages
- 40174-40184
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2004361822
- Cited by
- 606
- References
- 47
- FWCI
- 16.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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