OR01

Mycobacterium tuberculosis (M. tb) is the causative agent of human tuberculosis (TB) whereas Mycobacterium bovis and Mycobacterium orygis are the cattle-associated lineages. Unlike M. bovis, there is limited knowledge of M. orygis and its capacity to infect and cause disease. To address this gap, we  developed an experimental M. orygis infection model. We compared the infection outcome in C57BL/6 mice after aerosol exposure to M. tb H37Rv and M. orygis 51145. Unlike M. tb, where experimental infection is monitored at days 21, 42 and 84, the M. orygis group experienced mortality as early as 21 days. Macroscopically lungs showed significant inflammation and granuloma-like structures; histopathology showed extensive neutrophilic consolidation and destruction of airways. M. tb and M. orygis bacterial burden at this time point were comparable. We determined that at ~150 bacteria, the M. orygis survival has a bimodal distribution, with early (~4 weeks) and late (~4 months) waves of mortality. While M. orygis had a similar infection time-course as M. bovis Ravanel, to achieve this same distribution using M. tb we required > 1200 CFUs. Lastly, we were also able to delay mortality following subcutaneous vaccination with M. bovis BCG from ~4 weeks to ~4 months. In synopsis, M. orygis is a unique lineage of the MTBC.  Despite a distinct genomic identity from M. bovis, M. orygis has similar hyper-virulence following experimental murine infection. Further characterization of animal-associated and human-associated disease is required to better understand this overlooked pathogen.