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Overexpression of DosR in Mycobacterium tuberculosis does not affect aerobic replication in vitro or in murine macrophages

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Abstract

Mycobacterium tuberculosis H37Rv, constitutively expressing a second copy of the transcriptional regulator DosR (Rv3133c) under control of the hsp60 promoter, was compared to wild-type M. tuberculosis for in vitro expression of the target genes of the DosR dormancy regulon, for its in vitro growth characteristics in liquid 7H9 culture medium, and for its capacity to replicate in murine macrophages. Under aerobic conditions, hsp60-driven DosR significantly induced the expression of 39 out of 44 DosR regulon genes, as assessed by real time qPCR. Increased DosR regulon gene transcription in vitro did not modify the capacity of the strain to grow under axenic conditions nor to infect murine macrophages as compared to unmodified wild-type bacteria.

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Acknowledgments

This work was partially funded by grants of FWO-Vlaanderen (G.0376.05 [KH], Krediet aan Navorsers [MR] and G.0063.09 [DH]) by European Union (FP6-TBVAC and FP7-NEWTBVAC). D. Freches holds a FRIA bursary. Kirk Allen helped with statistical analysis of growth curves.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Stanford University School of Medicine, 450 Serra Mall, Stanford, CA, 94305, USA

    Mario Alberto Flores-Valdez, Gary Schoolnik & Gregory Dolganov

  2. Scientific Institute of Public Health-Site Ukkel Scientific Service Immunology, Brussels, Belgium

    Danielle Freches, Nicolas Bruffaerts, Marta Romano & Kris Huygen

  3. Biotecnología Médica y Farmacéutica CIATEJ, A.C., Av Normalistas No. 800 Col. Colinas de la Normal, 44270, Guadalajara, Jalisco, Mexico

    Mario Alberto Flores-Valdez

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  1. Mario Alberto Flores-Valdez
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  2. Danielle Freches
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  3. Nicolas Bruffaerts
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  4. Marta Romano
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  5. Gary Schoolnik
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  6. Gregory Dolganov
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  7. Kris Huygen
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Correspondence to Mario Alberto Flores-Valdez or Kris Huygen.

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Flores-Valdez, M.A., Freches, D., Bruffaerts, N. et al. Overexpression of DosR in Mycobacterium tuberculosis does not affect aerobic replication in vitro or in murine macrophages. Ann Microbiol 65, 713–720 (2015). https://doi.org/10.1007/s13213-014-0910-3

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  • DOI: https://doi.org/10.1007/s13213-014-0910-3

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