Booth Id:
BCHM021
Category:
Biochemistry
Year:
2020
Finalist Names:
Courcelle, Eleanor (School: Franklin High School)
Abstract:
The chemotherapeutic, hydroxyurea (HU), is an antimetabolite drug generally used to
treat chronic myelocytic leukemia as well as HIV and sickle cell anemia. Although initial
hydroxyurea therapy is often successful, its effectiveness frequently decreases with
sustained use due to the development of drug resistance, resulting in further expansion
of disease and patient death. Cellular expressions of catalases have been implicated in
regulating the response to HU, however the exact mechanism(s) by which cells develop
resistance to HU is unclear. This study aimed to develop a bacterial model in order to
determine the genes involved in the development of HU resistance. Similar to what has
been observed in eukaryotes, expression of bacterial catalases (encoded by katE and
katG genes) in Escherichia coli affected cells’ HU susceptibility, demonstrating that E. coli
is an appropriate model system for studying HU resistance. Following serial rounds of
exposure to HU and selection for resistant cells, an evolved strain of E. coli with
approximately 100,000-fold increase in survival rate when compared to the parent strain
was obtained. It was found that resistance to HU developed in a stepwise progression,
suggesting that there are multiple pathways involved in the acquisition of cell resistance
to this therapy. Future research will be directed at deep sequencing the genome of this
mutant E. coli strain and separately evolving other isolates of HU hyper-resistant E. coli, in
order to identify shared mutant genes that can then be screened to determine their role
in the development of cell resistance to HU.