The Effects of Functional Variability of M. smegmatis on Rifampicin Tolerance.
Richardson, Kirill.
2015
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Abstract:
Tuberculosis remains the world's second deadliest infectious disease after HIV/AIDS, and
poses a major threat to public health in many parts of the world. It has previously been
demonstrated that mycobacterial colonies exhibit distinct heterogeneous phenotypes, and
that this functional variation creates sub-populations of cells with differential
susceptibility to antibiotics. In this ... read morethesis, we investigated the effects of functional
variability of M. smegmatis bacteria on antibiotic tolerance. With the use of live-cell
microscopy system that combines imaging, microfluidics, and computational image
processing we separated an M. smegmatis bulk population into sub-populations with
distinct phenotypic characteristics. We then evaluated the response of these
sub-populations to rifampicin. We found that there was a correlation between rifampicin
tolerance and cell size, cell age, and cell cycle stage. We then conducted PLSR analysis
to determine the relative importance of various functional parameters to the rifampicin
tolerance. Finally, we created a compartmentalized model framework that is capable of
describing the pharmacodynamics of distinct bacterial sub-populations, and could be used
to quantitatively resolve single-cell and population-level
measurements.
Thesis (M.S.)--Tufts University, 2015.
Submitted to the Dept. of Biomedical Engineering.
Advisor: Bree Aldridge.
Committee: Lauren Black, and Nikhil Nair.
Keyword: Biomedical engineering.read less - ID:
- x633fc822
- Component ID:
- tufts:21513
- To Cite:
- TARC Citation Guide EndNote
