Pathogenesis of Mycobacterium tuberculosis and its Interaction with the Host Organism

Volume 374 of the series Current Topics in Microbiology and Immunology pp 81-108


Antimicrobial Efflux Pumps and Mycobacterium tuberculosis Drug Tolerance: Evolutionary Considerations

  • John D. SzumowskiAffiliated withDepartment of Medicine (Division of Infectious Diseases), University of Washington Email author 
  • , Kristin N. AdamsAffiliated withDepartment of Microbiology, University of Washington
  • , Paul H. EdelsteinAffiliated withDepartments of Pathology, Laboratory Medicine, and Medicine (Division of Infectious Diseases), University of Pennsylvania
  • , Lalita RamakrishnanAffiliated withDepartment of Medicine (Division of Infectious Diseases), University of WashingtonDepartment of Microbiology, University of WashingtonDepartment of Immunology, University of Washington

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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.