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Strain Variation in the Mycobacterium tuberculosis Complex: Its Role in Biology, Epidemiology and Control pp 247–262Cite as

DNA Replication Fidelity in the Mycobacterium tuberculosis Complex

Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 1019)

Abstract

Mycobacterium tuberculosis is genetically isolated, with no evidence for horizontal gene transfer or the acquisition of episomal genetic information in the modern evolution of strains of the Mycobacterium tuberculosis complex. When considered in the context of the specific features of the disease M. tuberculosis causes (e.g., transmission via cough aerosol, replication within professional phagocytes, subclinical persistence, and stimulation of a destructive immune pathology), this implies that to understand the mechanisms ensuring preservation of genomic integrity in infecting mycobacterial populations is to understand the source of genetic variation, including the emergence of microdiverse sub-populations that may be linked to the acquisition of drug resistance. In this chapter, we focus on mechanisms involved in maintaining DNA replication fidelity in M. tuberculosis, and consider the potential to target components of the DNA replication machinery as part of novel therapeutic regimens designed to curb the emerging threat of drug-resistance.

Keywords

  • Mutation rate
  • DNA polymerase
  • PHP domain
  • Drug resistance

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Acknowledgements

This work was supported by a subcontract from the US National Institute of Child Health and Human Development (NICHD) U01HD085531-02 (to D.F.W.); the South African Medical Research Council (to V.M.); the National Research Foundation of South Africa (to D.F.W. and V.M.); a Senior International Research Scholars grant from the Howard Hughes Medical Institute (to V.M.); a Helen Hay Whitney fellowship (to J.M.R.); an NIH Director’s New Innovator Award 1DP20D001378 (to S.F.), and a subcontract from NIAID U19 AI107774-0 (to S.F.).

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Authors and Affiliations

  1. MRC/NHLS/UCT Molecular Mycobacteriology Research Unit and DST/NRF Centre of Excellence for Biomedical TB Research, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, P/Bag X3, Rondebosch, 7700, South Africa

    Digby F. Warner & Valerie Mizrahi

  2. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA

    Jeremy M. Rock & Sarah M. Fortune

  3. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Sarah M. Fortune

  4. Ragon Institute of Massachusetts General Hospital, Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA

    Sarah M. Fortune

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  1. Digby F. Warner
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  2. Jeremy M. Rock
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  3. Sarah M. Fortune
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  4. Valerie Mizrahi
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Correspondence to Digby F. Warner or Valerie Mizrahi .

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  1. Swiss Tropical & Public Health Institute, University of Basel, Basel, Switzerland

    Sebastien Gagneux

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Warner, D.F., Rock, J.M., Fortune, S.M., Mizrahi, V. (2017). DNA Replication Fidelity in the Mycobacterium tuberculosis Complex. In: Gagneux, S. (eds) Strain Variation in the Mycobacterium tuberculosis Complex: Its Role in Biology, Epidemiology and Control. Advances in Experimental Medicine and Biology, vol 1019. Springer, Cham. https://doi.org/10.1007/978-3-319-64371-7_13

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