Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/10/2007
Publication Date: 12/3/2007
Citation: Seth, M., Vulchanova, L., Palmer, M.V., Waters, W.R., Sreevatsan, S. 2007. Proteomics Based Biomarker Discovery to Aid in the Unambiguous Detection of Bovine Tuberculosis Infection in Cattle [abstract]. Conference of Research Workers in Animal Diseases. p. 10P. Interpretive Summary:
Technical Abstract: Bovine Tuberculosis (TB) is a zoonotic infection caused by Mycobacterium bovis (MBO), a member of the Mycobacterium tuberculosis complex. The disease is generally asymptomatic with a long incubation period and good early diagnostics are lacking. Current surveillance for bovine TB is a laborious multistep testing protocol performed by a USDA accredited veterinarian administering a caudal fold skin test. Because a response to the caudal fold test is not specific for MBO, more accurate testing is required to differentiate MBO infections from cross reactions with other environmental mycobacterial exposures or infections. The confirmatory test is either a comparative cervical test or a test for gamma-interferon production in response to MBO antigens by blood leukocytes. The gamma-interferon assay requires that the blood samples be processed within 24 hours of collection and the test is relatively costly. Thus there is a need to develop a low cost, infection detection assay for bovine tuberculosis. We hypothesized that the serum protein profiles of the animals exposed to MBO are significantly different compared with naïve-unexposed animals. We tested this hypothesis on a set of sera collected from an experimental MBO infection study that included prospective samples from baseline to terminal tuberculosis infection. Uninfected contemporaneous controls served as "true" negatives in this study. We used a liquid chromatography followed by tandem mass spectrometry approach termed iTRAQ that allows identification and quantification of peptides between multiple sample groups. A total of 130 proteins were identified with a P-value less than or equal to 0.05. Of these, 5 major proteins were identified - Vitamin D binding protein precursor, alpha-1 acid glycoprotein, alpha-1B glycoprotein, and apolipoprotein A-1. All 5 proteins are involved in innate immune responses to mycobacterial infections and were significantly elevated in infected animals. Further studies to corroborate our current findings in a natural infection of bovine tuberculosis are in progress.