Confinement-Induced Drug-Tolerance in Mycobacteria Mediated by an Efflux Mechanism

A considerable challenge in controlling Tuberculosis (TB) disease is the prolonged multidrug chemotherapy required to overcome drug-tolerant mycobacteria that persist in human tissues. An essential component of TB infection involves intracellular Mycobacterium tuberculosis bacteria that multiply within macrophages and are significantly more tolerant to antibiotics compared to extracellular mycobacteria. To investigate this aspect of human TB, researchers created a physical cell culture system that mimics confinement of replicating mycobacteria, such as in a macrophage during infection. Using this system, they uncovered an epigenetic drug-tolerance phenotype that appears when mycobacteria are cultured in space-confined bioreactors and disappears in larger volume growth contexts. Efflux mechanisms that are induced in space-confined growth environments contribute to this drug-tolerance phenotype. Therefore, macrophage-induced drug tolerance by mycobacteria may be an effect of confined growth among other macrophage-specific mechanisms.
Source :      2015/8/29 10:41

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