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Experiments in the late 19th century sought to define the host specificity of the causative agents of tuberculosis in mammals.  Mycobacterium tuberculosis , the human tubercle bacillus, was independently shown by Smith, Koch, and von Behring to be avirulent in cattle. This finding was erroneously used by Koch to argue the converse, namely that  Mycobacterium bovis , the agent of bovine tuberculosis, was avirulent for man, a view that was subsequently discredited. However, reports in the literature of  M. tuberculosis  isolation from cattle with tuberculoid lesions suggests that the virulence of  M. tuberculosis  for cattle needs to be readdressed. We used an experimental bovine infection model to test the virulence of well-characterized strains of  M. tuberculosis  and  M. bovis  in cattle, choosing the genome-sequenced strains  M. tuberculosis  H37Rv and  M. bovis  2122/97. Cattle were infected with approximately 10 6  CFU of  M. tuberculosis  H37Rv or  M. bovis  2122/97, and sacrificed 17 weeks post-infection. IFN-γ and tuberculin skin tests indicated that both  M. bovis  2122 and  M. tuberculosis  H37Rv were equally infective and triggered strong cell-mediated immune responses, albeit with some indication of differential antigen-specific responses. Postmortem examination revealed that while  M. bovis  2122/97–infected animals all showed clear pathology indicative of bovine tuberculosis, the  M. tuberculosis –infected animals showed no pathology. Culturing of infected tissues revealed that  M. tuberculosis  was able to persist in the majority of animals, albeit at relatively low bacillary loads. In revisiting the early work on host preference across the  M. tuberculosis  complex, we have shown  M. tuberculosis  H37Rv is avirulent for cattle, and propose that the immune status of the animal, or genotype of the infecting bacillus, may have significant bearing on the virulence of a strain for cattle. This work will serve as a baseline for future studies into the genetic basis of host preference, and in particular the molecular basis of virulence in  M. bovis .

Revisiting Host Preference in the Mycobacterium tuberculosis Complex: Experimental Infection Shows M. tuberculosis H37Rv to Be Avirulent in Cattle