To: The George Mason University Community
Candidate: Sarah Hamer
Program: Master of Science in Biology
Date: Wednesday August 15, 2012
Time: 2:00 p.m.
Place: George Mason University, Prince William campus
Bull Run Hall, Room 247
Thesis Chair: Dr. Serguei Popov
Thesis Director: Dr. Myung-Chul Chung
Title: "The S-nitrosylation of Peroxiredoxin 1 during Bacillus anthracis Infection in Human Small Airway Epithelial Cells"
A copy of the thesis
is on reserve
in the Johnson Center
Library, Fairfax campus.
The thesis will not be read at the meeting, but should be
in advance. All members of the George Mason University community are
Bacillus anthracis, a Gram-positive soil bacterium,
is the causative agent of anthrax. B. anthracis is classified as a
“Category A” agent by the Centers for Disease Control and Prevention.
Although the key virulence factors of anthrax are the toxins (i.e.
lethal toxin and edema toxin), it has been proven that the bacterial
nitric oxide synthase (bNOS) of B. anthracis also plays a role in
pathogenesis. Since B. anthracis infection produces nitric oxide that
is responsible for S-nitrosylation of host proteins, it was
hypothesized that bNOS-induced nitric oxide contributes to the
regulation of functions in host cells through modifications of
proteins. Nitroproteomic analysis using the biotin switch technique
demonstrated that during B. anthracis infection, peroxiredoxin 1 (Prx1)
in human small airway epithelial cells (HASECs) was predominantly
S-nitrosylated. When Prx1 was S-nitrosylated, there was a decrease in
its peroxidase activity and an increase in its chaperone activity.
Treatment with a nitric oxide donor to ensure that proteins were
S-nitrosylated showed that in an environment that contained hydrogen
peroxide, S-nitrosylation contributed to a decrease in cell viability.
However, during early B. anthracis infection, S-nitrosylation of HSAECs
proteins increased cell viability, presumably due to Prx1 increased
chaperone activity when S-nitrosylated. It can be concluded that
during the early stages of B. anthracis infection, nitric oxide
produced by B. anthracis causes the S-nitrosylation of Prx1, which may
contribute to an early stage protection (an increase in viability) of