Antimicrobial efflux pumps and Mycobacterium tuberculosis drug tolerance: evolutionary considerations

• Published in: Current topics in microbiology and immunology Vol. 374; p. 81
• Main Authors: Szumowski, John D, Adams, Kristin N, Edelstein, Paul H, Ramakrishnan, Lalita
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2013
• Subjects: Antitubercular Agents - pharmacology; ATP-Binding Cassette Transporters - antagonists & inhibitors; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological Transport; Calcium Channel Blockers - pharmacology; Drug Resistance, Multiple, Bacterial - drug effects; Drug Synergism; Evolution, Molecular; Gene Expression; Humans; Macrophages - drug effects; Macrophages - microbiology; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Time Factors; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - microbiology; Verapamil - pharmacology; Virulence Factors - antagonists & inhibitors; Virulence Factors - genetics; Virulence Factors - metabolism
• ISSN: 0070-217X
• DOI: 10.1007/82_2012_300

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.