Antimicrobial Efflux Pumps and Mycobacterium tuberculosis Drug Tolerance: Evolutionary Considerations

  • John D. Szumowski
  • Kristin N. Adams
  • Paul H. Edelstein
  • Lalita Ramakrishnan


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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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • John D. Szumowski
    • 1
  • Kristin N. Adams
    • 2
  • Paul H. Edelstein
    • 3
  • Lalita Ramakrishnan
    • 1
    • 2
    • 4
  1. 1.Department of Medicine (Division of Infectious Diseases)University of WashingtonSeattleUSA
  2. 2.Department of MicrobiologyUniversity of WashingtonSeattleUSA
  3. 3.Departments of Pathology, Laboratory Medicine, and Medicine (Division of Infectious Diseases)University of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of ImmunologyUniversity of WashingtonSeattleUSA

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