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Deregulation of Genes Associated with Alternate Drug Resistance Mechanisms in Mycobacterium tuberculosis

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Abstract

Alternate mechanisms of drug resistance involving intrinsic defense pathways play an important role in development of drug resistance. Deregulation of drug efflux, cellular metabolism, and DNA repair have been indicated to have effect on drug tolerance and persistence. Here we chose eight genes from these pathways to investigate their association with development of multidrug resistance (MDR). We generated mono drug resistant and MDR strains of rifampicin and isoniazid and examined the differential expression of genes belonging to efflux, DNA repair and cell wall lipid synthesis pathways. Rv1687c, recB, ppsD and embC genes showed significant (P <0.05) upregulation in mono-resistant (both rifampicin and isoniazid) as well as MDR strains. mmr showed significant upregulation with rifampicin resistance while Rv1457c showed significant upregulation only with mono-resistant strains. Highest expression change was observed with Rv1687c and ppsD. The study identified potential key genes that are significantly associated with development of drug resistance in vitro. These genes may help identify clinical strains predisposed to acquiring drug resistance in patients during the course of treatment or help in management of MDR forms of tuberculosis.

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Acknowledgements

This work was supported by Department of Science and Technology, Government of India [SB/SO/HS-0065/2013]. The authors thank Ms Rupali Kekane for her technical assistance in performing line probe assays.

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Authors and Affiliations

  1. The Foundation for Medical Research, 84-A, R.G. Thadani Marg, Worli, Mumbai, 400 018, India

    Kalpana Sriraman, Kayzad Nilgiriwala, Dhananjaya Saranath, Anirvan Chatterjee & Nerges Mistry

  2. Molecular Virology Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Powai, Mumbai, 400076, India

    Anirvan Chatterjee

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  1. Kalpana Sriraman
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  2. Kayzad Nilgiriwala
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  3. Dhananjaya Saranath
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Correspondence to Nerges Mistry.

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Sriraman, K., Nilgiriwala, K., Saranath, D. et al. Deregulation of Genes Associated with Alternate Drug Resistance Mechanisms in Mycobacterium tuberculosis . Curr Microbiol 75, 394–400 (2018). https://doi.org/10.1007/s00284-017-1393-9

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  • DOI: https://doi.org/10.1007/s00284-017-1393-9

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