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Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD

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Abstract

The mycobacterial FASII multi-enzyme complex has been identified to be a target of Ser/Thr protein kinases (STPKs) of Mycobacterium tuberculosis (MTB), with substrates, including the malonyl-CoA:ACP transacylase (FabD) and the β-ketoacyl-ACP synthases KasA and KasB. These proteins are phosphorylated by various kinases in vitro. The present study links the correlation of FASII pathway with serine threonine protein kinase of MTB. In the preliminary finding, we have shown that mycobacterial protein Rv3080c (PknK) phosphorylates FabD and the knockdown of PknK protein in mycobacteria down regulates FabD expression. This event leads to the differential inhibition of mycobacteria in the presence of isoniazid (INH), as the inhibition of growth of mycobacteria in the presence of INH is enhanced in PknK deficient mycobacteria.

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Acknowledgments

This study was supported in parts by network project grant SPLENDID from Council of Scientific and Industrial Research, New Delhi. We thank Director, CDRI for his encouragement and support. RK is recipient of ICMR Fellowship. This is CDRI communication # 8347.

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Authors and Affiliations

  1. Department of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226001, India

    Ruma Kumari, Richa Saxena, Sameer Tiwari, Dinesh K. Tripathi & Kishore K. Srivastava

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  1. Ruma Kumari
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  2. Richa Saxena
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  3. Sameer Tiwari
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  4. Dinesh K. Tripathi
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  5. Kishore K. Srivastava
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Correspondence to Kishore K. Srivastava.

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Kumari, R., Saxena, R., Tiwari, S. et al. Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD. Mol Cell Biochem 374, 149–155 (2013). https://doi.org/10.1007/s11010-012-1514-5

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  • DOI: https://doi.org/10.1007/s11010-012-1514-5

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