AbstractTheMycobacterium tuberculosiscomplex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported thatM. tuberculosisH37Rv, a standard reference MTBC strain, is attenuated in cattle compared toMycobacterium bovis. However, asM. tuberculosisH37Rv was isolated in the early 1930s, and genetic variants are known to exist, we sought to revisit this question of attenuation ofM. tuberculosisfor cattle by performing a bovine experimental infection with a recentM. tuberculosisisolate. Here we report infection of cattle usingM. bovisAF2122/97,M. tuberculosisH37Rv, andM. tuberculosisBTB1558, the latter isolated in 2008 during a TB surveillance project in Ethiopian cattle. We show that bothM. tuberculosisstrains caused reduced gross and histopathology in cattle compared toM. bovis. UsingM. tuberculosisH37Rv andM. bovisAF2122/97 as the extremes in terms of infection outcome, we used RNA-Seq analysis to explore differences in the peripheral response to infection as a route to identify biomarkers of progressive disease in contrast to a more quiescent, latent infection. Our work shows the attenuation ofM. tuberculosisstrains for cattle, and emphasizes the potential of the bovine model as a ‘One Health’ approach to inform human TB biomarker development and post-exposure vaccine development.
Genetic control of resistance to experimental infection with virulent Mycobacterium tuberculosis