Discovery of infectious disease biomarkers in murine anthrax model using mass spectrometry of the low-molecular-mass serum proteome

Aarthi Narayanan, Weidong Zhou, Mark Ross, Jane Tang, Lance Liotta, Emanuel Petricoin, Fatah Kashanchi, Charles Bailey, Serguei Popov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)408-415
Number of pages8
JournalJournal of Proteomics and Bioinformatics
Volume2
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

Keywords

  • Anthrax
  • Biomarkers
  • Mass spectrometry
  • Proteome

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