Abstract

Antemortem tests for bovine tuberculosis (bTB) currently used in the US measure cell-mediated immune responses against Mycobacterium bovis. Postmortem tests for bTB rely on observation of gross and histologic lesions of bTB, followed by bacterial isolation or molecular diagnostics. Cumulative data from the state of Michigan indicates that 98 to 99% of cattle that react positively in antemortem tests are not confirmed positive for bTB at postmortem examination. Understanding the fundamental differences in gene regulation between antemortem test-false positive cattle and cattle that have bTB may allow identification of molecular markers that can be exploited to better separate infected from noninfected cattle. An immunospecific cDNA microarray was used to identify altered gene expression (P ≤ 0.01) of 122 gene features between antemortem test-false positive cattle and bTB-infected cattle following a 4-hour stimulation of whole blood with tuberculin. Further analysis using quantitative real-time PCR assays validated altered expression of 8 genes that had differential power (adj P ≤ 0.05) to segregate cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis.

Highlights

  • Bovine tuberculosis caused by Mycobacterium bovis (M. bovis) occurs worldwide and has been estimated to cause annual losses of three billion dollars to global agriculture [1, 2]

  • Further analysis using quantitative real-time polymerase chain reaction (PCR) assays validated altered expression of 8 genes that had differential power to segregate cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis

  • In Michigan, the current rate of bTBinfection is extremely low, which leads to far more antemortem test-false positive cattle being culled as bTB suspects than the number of bTB infected cattle identified at postmortem examination

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Summary

Introduction

Bovine tuberculosis (bTB) caused by Mycobacterium bovis (M. bovis) occurs worldwide and has been estimated to cause annual losses of three billion dollars to global agriculture [1, 2]. In addition to being an important pathogen of cattle, M. bovis may infect many other domestic and wildlife species, and it infects humans [3,4,5]. Control of bTB is a continuing effort that is necessary to protect livestock, wildlife, and human populations. Control of bTB is based on “test and slaughter” programs. Field and/or laboratory diagnostic tests are used to identify potentially infected cattle herds for quarantine, which may be followed by additional diagnostic testing and slaughter of all cattle that show positive test reactions. “test and slaughter” programs are costly and have not been adopted by most developing countries

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