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Author:
Campoesco Jacobs, Ana Lucia
Dept./Program:
Biomedical Engineering Program
Year:
2014
Degree:
M.S.
Abstract:
Resistance to antibiotics has become a major public-health threat, with resistant strains of bacteria emerging shortly after the introduction of penicillin. Bacteria can increase their tolerance to antibiotics in different ways. One way is via inherited genetic modifications, for instance mutations or acquisition of plasmids. However, they can also increase their tolerance through transient non-genetic mechanisms that allow cells to induce expression ofresistance genes temporarily.
We focus our research on the multiple antibiotic resistance (mar) network of Escherichia coli as a model for transient resistance. The mar network is composed of more than 40 genes, many of which are implicated in resistance to antibiotics. This network is regulated by the three transcription factors, MarA, SoxS, and Rob, but antibiotic resistance is primarily derived from MarA. We experimentally quantify noise in the expression of the mar operon at single cell resolution and show that there is significant variability within the population. We then observe the, difference in noise dynamics in cells with the mar operon present or absent, as well as the contributions to the noise by sox and rob. Finally, we present initial data measuring the propagation of noise in marA to other genes in the mar network (inaA, micF and acrAB) and discuss implications in the generation of different antibiotic resistance phenotypes.