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Genome-Wide Expression Profiling of the Response to Linezolid in Mycobacterium tuberculosis

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Abstract

Tuberculosis (TB) is still one of the most common causes of death in the world. The emergence of multidrug-resistant and extensively drug-resistant (XDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has increased the importance of searching for alternative targets to develop new antimycobacterial drugs. Linezolid, the first of oxazolidinones, is active in vitro against M. tuberculosis, but the response mechanisms of M. tuberculosis to linezolid are still poorly understood. To reveal the possible mechanism of action of linezolid against M. tuberculosis, commercial oligonucleotide microarrays were used to analyze the genome-wide transcriptional changes triggered by treatment with subinhibitory concentrations of linezolid. Quantitative real-time RT-PCR was performed for selected genes to verify the microarray results. A total of 729 genes were found to be differentially regulated by linezolid. Among these, 318 genes were upregulated, and 411 genes were downregulated. A number of important genes were significantly regulated that are involved in various pathways, such as protein synthesis, sulfite metabolism, and genes involved in the cell envelope and virulence. This genome-wide transcriptomics approach produced the first insights into the response of M. tuberculosis to a linezolid challenge.

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Acknowledgments

Financial supports for this work came from the Doctoral Program of Higher Education (SRFDP) (No. 200801831051), the Specialized Research Fund for Important National Science & Technology Specific Projects (2012ZX10003002-001), the Fund for Science and Technology Development of the Jilin Province, China (No. 20080565), National Nature Science Foundation of China (No. 31172364), Shenzhen biological special funds for industrial development aid key basic research project (JC201005280643A), and the Fundamental Research Funds for the Central Universities.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, People’s Republic of China

    Junchao Liang, Xiuping Wu, Xuelin Wang, Zhenhong Guan, Lihui Liu, Fengge Shen, Mingxun Xing, Lei Li & Lu Yu

  2. Key Lab for New Drug Research of TCM, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, People’s Republic of China

    Xudong Tang

  3. Department of Food Quality and Safety, College of Quartermaster Technology, Jilin University, Changchun, 130062, People’s Republic of China

    Na Guo

  4. Department of Infectious Diseases, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China

    Kaiyu Zhang

  5. The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China

    Aizhen Guo & Liqiang Liu

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  1. Junchao Liang
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  2. Xudong Tang
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  3. Na Guo
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  9. Lihui Liu
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  12. Liqiang Liu
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  13. Lei Li
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  14. Lu Yu
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Correspondence to Lu Yu.

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Junchao Liang, Xudong Tang, Na Guo, Kaiyu Zhang, Aizhen Guo, Xiuping Wu, Xuelin Wang, and Zhenhong Guan equally contributed to this work.

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Liang, J., Tang, X., Guo, N. et al. Genome-Wide Expression Profiling of the Response to Linezolid in Mycobacterium tuberculosis . Curr Microbiol 64, 530–538 (2012). https://doi.org/10.1007/s00284-012-0104-9

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