Discovery of Infectious Disease Biomarkers in Murine
Anthrax Model Using Mass Spectrometry of the
Low-Molecular-Mass Serum Proteome |
| Aarthi Narayanan1, Weidong Zhou2, Mark Ross2, Jane Tang3, Lance Liotta2,
Emanuel Petricoin2, Fatah Kashanchi4, Charles Bailey1, Serguei Popov1 |
1National Center for Biodefense and Infectious Diseases |
2Center for Proteomics and Molecular Medicine, George Mason University,
10900 University Blvd,Manassas, Virginia – 20110-2201 |
3Noblis, 3150 Fairview Park Drive, Falls Church, Virginia – 22042 |
4The George Washington University, 2121 Street, NW, Washington, DC 20052 |
| *Corresponding author: |
Dr. Serguei Popov,
George Mason University,
10900 University Blvd, Manassas,
Virginia – 20110-2201,
Phone: 703 993
4713,
E-mail: spopov@gmu.edu |
|
| September 23, 2009; Accepted September 29, 2009; Published September 30, 20 |
Citation: Narayanan A, Zhou W, Ross M, Tang J, Liotta L, et al. (2009)
Discovery of Infectious Disease Biomarkers in Murine Anthrax Model
Using Mass Spectrometry of the Low-Molecular-Mass Serum Proteome.
J Proteomics Bioinform 2: 408-415. doi:10.4172/jpb.1000101 |
Copyright: ©2009 Narayanan A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author
and source are credited. |
| Abstract |
A novel mass spectrometry (MS)-based approach to
the identification of host-derived biomarkers (BMs) in
the circulating low-molecular-mass (LMM) fraction (<25
kDa) of blood proteome was tested in a murine model.
DBA2/J mice were challenged intraperitonially with
spores of either the toxigenic B. anthracis Sterne strain
(pXO1+, pXO2-) that is virulent in DBA/2 mice or the
nontoxigenic, non-virulent delta Sterne strain (pXO1-,
pXO2-). Serum samples were obtained at multiple time
points and seperated by continuous flow denaturing gel
electrophoresis followed by Coomassie staining to isolate
the LMM archive for subsequent MS identification.
Peptide fragments derived from more than 200 proteins
displayed low-variance differential abundances between
lethal and non-lethal challenges. Several proteins from
the MS analysis were subjected to secondary verification
by western blots. Serum abundances of 6 proteins
(carbonic anhydrase 2, adenylate kinase 1, peroxyredoxin
2, UMP-CMP kinase, Ras-related C3 botulinum substrate
1, and destrin) from a total of 10 tested proteins were
strongly coincident with established anthrax disease and
mortality thus making them potential candidates for hostderived
anthrax disease associated BMs. These BMs
were demonstrated to be “elastic” in that their abundance
levels in sera of doxycycline-treated mice responded to
the therapeutic intervention thus making them useful tools
for monitoring efficacies of existing and novel treatment
regimens. |
|
|
|