Circulating Mycobacterium bovis Peptides and Host Response Proteins as Biomarkers for Unambiguous Detection of Subclinical Infection

Abstract

e Bovine tuberculosis remains one of the most damaging diseases to agriculture, and there is also a concern for human spillover. A critical need exists for rapid, thorough, and inexpensive diagnostic methods capable of detecting and differentiating Mycobacterium bovis infection from other pathogenic and environmental mycobacteria at multiple surveillance levels. In a previous study, Seth et al. (PLoS One 4:e5478, 2009, doi:10.1371/journal.pone.0005478) identified 32 host peptides that specifically increased in the blood serum of M. bovis-infected animals). In the current study, 16 M. bovis proteins were discovered in the blood serum proteomics data sets. A large-scale validation analysis was undertaken for selected host and M. bovis proteins using a cattle serum repository containing M. bovis (n ‫؍‬ 128), Mycobacterium kansasii (n ‫؍‬ 10), and Mycobacterium avium subsp. paratuberculosis (n ‫؍‬ 10), cases exposed to M. bovis (n ‫؍‬ 424), and negative controls (n ‫؍‬ 38). Of the host biomarkers, vitamin D binding protein (VDBP) showed the greatest sensitivity and specificity for M. bovis detection. 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. These data indicate that host and pathogen serum proteins can serve as reliable biomarkers for tracking M. bovis infection in animal populations.

Mannosylated lipoarabinomannan in serum as a biomarker candidate for subclinical bovine tuberculosis

“…We have shown that mycobacterial peptides circulating in the serum accurately predict bTB infected from bTB negative and exposed animals [9]. We have extended our previous study to investigate another mycobacterial related component, LAM, likely present in serum of bTB infected animals, which may be used with additional pathogen signatures to provide a battery test for subclinical bTB.…”

A bloody evidence: IsMycobacterium bovisbacteraemia frequent in cattle?!

“…Such responses may be influenced by previous exposure to other mycobacterial agents, as a high level of homology exists among mycobacterial species. 3 The current testing limitations and the significant economic losses that ensue, as well as the risk of transmission among livestock, human and wildlife emphasize the desperate need for rapid and inexpensive diagnostic methods able to detect and distinguish M. bovis infection from other pathogenic and environmental mycobacteria. [1][2][3][4] More specific diagnostic tests, relying on the identification of the pathogen or its antigens, have proven to be challenging.…”

“…[10][11][12] The success level of culture can be determined by the growth rates, the inability of potential isolates to adapt to in-vitro culture conditions, especially in situations where the number of bacilli are limiting, which could result in false-negative results by culture. 3,5,9 Also, for bTB in cattle, culture of tissues collected post-mortem is often used to confirm infection. Mycobacteraemia occurrence in infected animals by itself is not sufficient to make blood culture a valuable diagnostic test for bTB, as the long period needed for culture would still hinder its use as a screening test.…”

Fractionation and Analysis of Mycobacterial Proteins

“…In addition, emerging and reemerging diseases and public health concerns regarding a rise in pulmonary and cutaneous nontuberculous mycobacteria (NTM, [ 19 , 20 ]) and economic impact of mycobacterial infections of livestock [ 15 ], requires the use of established biochemical and proteomics methodologies to extend studies into these understudied and important pathogens.…”