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Title:   Author  item
                                            SETH, MEETU - UNIV. OF MNitem
                                            JANAGAMA, HARISH - UNIV. OF MNitem
                                            LAMONT, ELISE - UNIV. OF MNitem
                                            WIDDEL, ANDREA - UNIV. OF MNitem
                                            VULCHANOVA, LUCY - UNIV. OF MNitem
                                            Stabel, Judithitem
                                            Waters, Wadeitem
                                            Palmer, Mitchellitem
                                            SREEVATSAN, SRINAND - UNIV. OF MN
  Submitted to: PLOS ONE
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/9/2009
                                    Publication  Date: 5/8/2009
                                    Citation: Seth, M., Janagama, H.K., Lamont, E.A., Widdel, A., Vulchanova, L., Stabel, J.R., Waters, W.R., Palmer, M.V., Sreevatsan, S. 2009. Biomarker Discovery in Subclinical Mycobacterial Infections of Cattle. PLoS One [serial online]. 4(5):e5478. Available: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005478.Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. Johne’s disease of cattle is ubiquitous causing serious economic losses to the dairy industry due to decreased health and production of affected animals. Together, these two related disease cause serious economic hardships for cattle producers. Improved techniques are needed for detection of both of these diseases in cattle as well as improved control strategies (e.g., vaccines). To develop improved tests and vaccines, it is beneficial to first understand the nature of the bovine immune response to the pathogens. In this study, proteins in the sera of tuberculosis- and Johne’s disease-infected cattle were evaluated. Unique signatures of infection were determined. This basic information will be useful for development of improved tests and vaccines for cattle; thereby, benefiting cattle producers.
                                Technical Abstract: Background: Bovine tuberculosis is a highly prevalent infectious disease of cattle worldwide; however, infection in the United States is limited to 0.01% of dairy herds.  Thus detection of bovine TB is confounded by high background infection with M. avium subsp. paratuberculosis. The present study addresses variations in the circulating peptidome based on the pathogenesis of two biologically similar mycobacterial diseases of cattle. Methodology/Principal Findings: We hypothesized that serum proteomes of animals in response to either M. bovis or M. paratuberculosis infection will display several commonalities and differences. Sera prospectively collected from animals experimentally infected with either M. bovis or M. paratuberculosis were analyzed using high-resolution proteomics approaches.  iTRAQ, a liquid chromatography and  tandem mass spectrometry approach, was used to   simultaneously  identify and quantify peptides  from multiple infections and contemporaneous uninfected control groups. Four comparisons were performed: 1) M. bovis infection versus uninfected controls, 2) M. bovis versus M. paratuberculosis infection, 3) early, and 4) advanced M. paratuberculosis infection versus uninfected controls. One hundred and ten differentially elevated proteins (P £ 0.05) were identified. Vitamin D binding protein precursor (DBP), alpha-1 acid glycoprotein, alpha-1B glycoprotein, fetuin, and serine proteinase inhibitor were identified in both infections. Transthyretin, retinol binding proteins, and cathelicidin were identified exclusively in M. paratuberculosis infection, while the serum levels of alpha-1-microglobulin/bikunin precursor (AMBP) protein, alpha-1 acid glycoprotein, fetuin, and alpha-1B glycoprotein were elevated exclusively in M. bovis infected animals. Conclusions/Significance: The discovery of these biomarkers has significant impact on the elucidation of pathogenesis of two mycobacterial diseases at the cellular and the molecular level and can be applied in the development of mycobacterium-specific diagnostic tools for the monitoring progression of disease, response to therapy, and/or vaccine based interventions.


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