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Pathogenesis of Mycobacterium tuberculosis and its Interaction with the Host Organism pp 81–108Cite as

Antimicrobial Efflux Pumps and Mycobacterium tuberculosis Drug Tolerance: Evolutionary Considerations

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 374))

Abstract

The need for lengthy treatment to cure tuberculosis stems from phenotypic drug resistance, also known as drug tolerance, which has been previously attributed to slowed bacterial growth in vivo. We discuss recent findings that challenge this model and instead implicate macrophage-induced mycobacterial efflux pumps in antimicrobial tolerance. Although mycobacterial efflux pumps may have originally served to protect against environmental toxins, in the pathogenic mycobacteria, they appear to have been repurposed for intracellular growth. In this light, we discuss the potential of efflux pump inhibitors such as verapamil to shorten tuberculosis treatment by their dual inhibition of tolerance and growth.

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Acknowledgments

JDS is supported by NIH T32 5T32AI007044-36 and the Merle A. Sande-Pfizer Fellowship in International Infectious Diseases. KNA is supported by NIH T32 AI55396. PHE is supported by NIH 5R18HS020002-03. LR is supported by grants from the NIH and is the recipient of the NIH Director’s Pioneer Award.

We thank Josh Woodward, Christine Cosma, and Mark Troll for helpful discussions and manuscript review.

Author information

Authors and Affiliations

  1. Department of Medicine (Division of Infectious Diseases), University of Washington, Seattle, WA, USA

    John D. Szumowski & Lalita Ramakrishnan

  2. Department of Microbiology, University of Washington, Seattle, WA, USA

    Kristin N. Adams & Lalita Ramakrishnan

  3. Departments of Pathology, Laboratory Medicine, and Medicine (Division of Infectious Diseases), University of Pennsylvania, Philadelphia, PA, USA

    Paul H. Edelstein

  4. Department of Immunology, University of Washington, Seattle, WA, USA

    Lalita Ramakrishnan

Authors
  1. John D. Szumowski
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  2. Kristin N. Adams
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  3. Paul H. Edelstein
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  4. Lalita Ramakrishnan
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Corresponding author

Correspondence to John D. Szumowski .

Editor information

Editors and Affiliations

  1. Biozentrum, University of Basel, Basel, Switzerland

    Jean Pieters

  2. Laboratory of Microbiology and Microsystems, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland

    John D. McKinney

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© 2012 Springer-Verlag Berlin Heidelberg

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Szumowski, J.D., Adams, K.N., Edelstein, P.H., Ramakrishnan, L. (2012). Antimicrobial Efflux Pumps and Mycobacterium tuberculosis Drug Tolerance: Evolutionary Considerations. In: Pieters, J., McKinney, J. (eds) Pathogenesis of Mycobacterium tuberculosis and its Interaction with the Host Organism. Current Topics in Microbiology and Immunology, vol 374. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2012_300

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