Abstract
The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was isolated in the early 1930s, and genetic variants are known to exist, we sought to revisit this question of attenuation of M. tuberculosis for cattle by performing a bovine experimental infection with a recent M. tuberculosis isolate. Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB surveillance project in Ethiopian cattle. We show that both M. tuberculosis strains caused reduced gross pathology and histopathology in cattle compared to M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 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 of M. tuberculosis strains 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.
Highlights
The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals
Because of the need to restrict the total time the experiment would run in the containment facility, animals infected with M. tuberculosis strains H37Rv or BTB1558 were maintained for 10 weeks, while M. bovis AF2122/97-infected animals were maintained for 6 weeks, after which all animals underwent post-mortem examination
This work set out to explore whether a recent isolate of M. tuberculosis, recovered from a TB lesion identified in an Ethiopian bull, would trigger a similar immunological and pathological response to the M. tuberculosis H37Rv reference strain when used to experimentally infect cattle
Summary
The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. Thirty-two strand-specific RNA-Seq libraries were prepared from whole blood from M. bovis AF2122/7 and M. tuberculosis H37Rv infected animals (n = 4) at day 14 and day TM 42 that were either stimulated or not with PPD-B.
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