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To: The George Mason University Community
Candidate: Sarah Hamer
Program: Master of Science in Biology
Date: Wednesday April 25, 2012
Time: 10:00 a.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 in Human Small Airway Epithelial Cells During Bacillus Anthracis Infection"
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 organism,
is the causative agent of anthrax. Although the key virulence factor
of anthrax is mediated by toxins (i.e. lethal toxin and edema toxin),
it has proven that the bacterial nitric oxide synthase (bNOS) of B.
anthracis, also, plays a role in pathogenesis. Since B. anthracis
infection produced bona fide nitric oxide that is responsible for
protein modification by S-nitrosylation, I hypothesized that
bNOS-induced nitric oxide contributes to regulation of host cell
function through protein chemical modification. The nitrosproteomic
analysis using the biotin-switch assay demonstrated that during B.
anthracis infection, peroxiredoxin 1 (Prx1) was predominantly
S-nitrosylated; there was a decrease in its peroxidase activity and an
increase in its chaperone activity, which both affect cell viability.
Treatment with a nitric oxide donor in a high hydrogen peroxide
environment decreased cell viability; while during B. anthracis there
was an increase in cell viability, presumably due to increase of
chaperone activity of Prx1. These results suggest that during B.
anthracis infection, bacteria-derived nitric oxide plays a role in
oxidative or nitrosative stress-induced epithelial responses to the
pathogen in the lung.