Detection of lipomannan in cattle infected with bovine tuberculosis

Authors: VU, DUNG - Los Alamos National Research Laboratory; SAKAMURI, RAMA - Los Alamos National Research Laboratory; Waters, Wade; SWANSON, BASIL - Los Alamos National Research Laboratory; MUKUNDAN, H - Los Alamos National Research Laboratory

Submitted to: Analytical Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/8/2017
Publication Date: 4/8/2017
Citation: Vu, D.M., Sakamuri, R.M., Waters, W.R., Swanson, B.I., Mukundan, H. 2017. Detection of lipomannan in cattle infected with bovine tuberculosis. Analytical Sciences. 33(4):457-460. doi: 10.2116/analsci.33.457.

Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, recent outbreaks of tuberculosis in various regions of the United States demonstrate that the disease is far from eliminated. Cattle are routinely tested for tuberculosis by tuberculin skin testing as outlined in the United States Department of Agriculture uniform methods and rules for the eradication of bovine tuberculosis. However, more convenient and specific tests are greatly needed. 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. In this study, a biological marker of infection was found in the sera of tuberculosis-infected cattle after experimental infection with M. bovis. Importantly, a novel and sensitive method was developed to detect the biological marker. These findings demonstrate the possibility for development of improved tests to detect tuberculous cattle.

Technical Abstract: Early and rapid detection of bovine tuberculosis (bTB) is critical to controlling the spread of this disease in cattle and other animals. In this study, we demonstrate the development of an immunoassay for the direct detection of the bovine bTB biomarker, lipomannan (LM) in serum using a waveguide-based optical biosensor. We apply an ultra-sensitive detection strategy developed by our team, termed lipoprotein capture, that exploits the pull-down of high density lipoprotein (HDL) nanodiscs from cattle blood that allowing for the recovery and detection of associated LM. We also profile the change in expression of these TB biomarkers as a function of time from a small set of samples collected from studies of bovine TB infected cattle. We demonstrate for the first time the direct detection of bovine LM in serum, and clearly show that the biomarker is expressed in detectable concentrations during the entire course of the infection.