Circulating Mycobacterium bovis peptides and host response proteins as biomarkers for unambiguous detection of subclinical infection

Authors: LAMONT, ELISE - University Of Minnesota; JANAGAMA, HARISH - Texas A&M University Health Science Center; RIBEIRO-LIMA, JOAO - University Of Minnesota; HART, LUCY - University Of Minnesota; SETH, MEETU - University Of Massachusetts; YANG, MY - University Of Minnesota; KUMI, KIRAN - University Of Minnesota; Waters, Wade; Thacker, Tyler; HARRIS, N - Animal And Plant Health Inspection Services (APHIS), National Wildlife Center; SREEVATSAN, SRINAND - University Of Minnesota

Submitted to: Journal of Clinical Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/26/2013
Publication Date: 2/1/2014
Publication URL: http://handle.nal.usda.gov/10113/58865
Citation: Lamont, E.A., Janagama, H.K., Ribeiro-Lima, J., Hart, L., Seth, M., Yang, M., Kumi, K., Waters, W.R., Thacker, T.C., Harris, N.B., Sreevatsan, S. 2014. Circulating Mycobacterium bovis peptides and host response proteins as biomarkers for unambiguous detection of subclinical infection. Journal of Clinical Microbiology. 52(2):536-543.

Interpretive Summary: Bovine tuberculosis (bTB), caused by Mycobacterium bovis, accounts for up to 10% of human TB cases in developing countries and is increasing in cattle in the US and UK. Control of bTB is hindered by the presence of numerous wildlife reservoirs such as white-tailed deer, European badgers, and brush-tailed possums. Reasons for the failure to eradicate the disease are multi-factorial; however, limitations in the availability of accurate and convenient tests are a primary factor. 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-infected cattle were evaluated. Unique signatures of infection were determined and several new markers of infection were characterized. This information will be useful for development of improved tests and vaccines for cattle; thereby, benefiting cattle producers.

Technical Abstract: Background: Bovine tuberculosis remains one of the most damaging zoonotic diseases. A critical need exists for rapid and inexpensive diagnostics capable of detecting and differentiating M. bovis infection from other pathogenic and environmental mycobacteria at multiple surveillance levels. Methods: In a previous study, Seth et al. identified 32 host peptides that specifically increased in the serum of M. bovis infected animals [1]. In the current study, 16 M. bovis proteins were discovered in the serum proteomics datasets. A large scale validation was undertaken for selected host and M. bovis proteins using a cattle serum repository containing M. bovis (n=128), M. kansasii (n=10), and M. avium subsp. paratuberculosis (n=10), exposed cases of M. bovis (n=424) and negative controls (n=38). Results: Of the host biomarkers, vitamin D binding protein (VDBP) showed the greatest sensitivity and specificity for M. bovis infection. Circulating M. bovis proteins, specifically polyketide synthetase 5, detected M. bovis infected cattle with little to no seroreactivity against M. kansasii and M. avium subsp. paratuberculosis infected animals. Conclusions: These data indicate that host and pathogen serum proteins can serve as reliable biomarkers for tracking M. bovis infection in animal populations and provide a novel approach to diagnosis of human tuberculosis.