Biophysical Society Thematic Meeting - November 16-20, 2015

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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts
92
22-POS Board 22
Confinement-Induced Drug-Tolerance in Mycobacteria Growing in Miniaturized
Bioreactors
Brilliant Luthuli1, Georgiana Purdy2, Frederick Balagadde 1.
1K-RITH, Durban, South Africa, 2Oregon 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.