Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts

22-POS Board 22 Confinement-Induced Drug-Tolerance in Mycobacteria Growing in Miniaturized Bioreactors Brilliant Luthuli 1 , Georgiana Purdy 2 , Frederick Balagadde 1 . 1 K-RITH, Durban, South Africa, 2 Oregon Health and Sciences University,, Portland, OR, USA. A considerable challenge in controlling tuberculosis is the prolonged multidrug chemotherapy (6 to 9 months) required to overcome drug-tolerant mycobacteria that persist in human tissues, although the same drugs can sterilize genetically identical mycobacteria growing in axenic culture within days. An essential component of TB infection involves intracellular Mycobacterium tuberculosis pathogens that multiply within macrophages and are significantly more tolerant to antibiotics compared to extracellular mycobacteria. We have developed the microdialyser, a new system of culturing mycobacteria in bioreactors with volume comparable to membrane-bound compartment of a macrophages. The microdialyser can support 120 independent cultures with mycobacterial populations ranging from one to over 1000 cells at the same time. Using this system we have uncovered an epigenetic drug-tolerating phenotype that appears when mycobacteria are cultured in the space-confined bioreactors but disappears in larger volume bioreactors. Therefore, macrophage-induced drug tolerance by mycobacteria may be an effect of growth in space confined environment among other macrophage-specific mechanisms.

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