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Drug Resistance in Bacteria, Fungi, Malaria, and Cancer pp 233–262Cite as

Implications of Chromosomal Mutations for Mycobacterial Drug Resistance

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Abstract

Tuberculosis (TB) remains a global health concern, despite availability of antituberculosis drugs. Drug-resistant Mycobacterium tuberculosis strains were identified shortly after the discovery and introduction of streptomycin for the treatment of this disease. Subsequently, multidrug therapy was implemented for TB treatment; however, this was soon followed by reports of multi-, extensively, and totally drug-resistant tuberculosis cases globally. The amplification of this drug resistance is due to the sequential accumulation of chromosomal alterations in target genes in the Mycobacterium tuberculosis genome. It is also evident that the presence of mutations that confer drug resistance results in the emergence of compensatory mechanisms which restore bacterial fitness. The recent approval by the Food and Drug Administration for bedaquiline as an antituberculosis drug provided some hope. However, clinical resistance to this new drug has already been reported. This underscores that it is imperative to understand drug resistance and its associated mechanisms in order to direct research efforts to the development of antituberculosis regimens with novel mechanisms of actions.

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Acknowledgements

This work was funded, in part, by the Intramural Research Program of the NIAID and by grants from the Foundation for the National Institutes of Health. SLS is funded by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa, award number UID 86539. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NRF.

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  1. Faculty of Health Sciences, Division of Medical Microbiology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa

    Gail E. Louw

  2. DST/NRF Centre of Excellence for Biomedical Tuberculosis Research/SA MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Stellenbosch, South Africa

    Samantha L. Sampson

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Correspondence to Gail E. Louw .

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  1. CSIR - Institute of Genomics and Integrative Biology, Delhi, India

    Gunjan Arora

  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Andaleeb Sajid

  3. CSIR - Institute of Genomics and Integrative Biology, Delhi, India

    Vipin Chandra Kalia

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Louw, G.E., Sampson, S.L. (2017). Implications of Chromosomal Mutations for Mycobacterial Drug Resistance. In: Arora, G., Sajid, A., Kalia, V. (eds) Drug Resistance in Bacteria, Fungi, Malaria, and Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-48683-3_10

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