M. orygis hypervirulence provides new insights into tuberculosis pathogenesis
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The Mycobacterium tuberculosis complex (MTBC) includes M. tuberculosis ( M. tb ), the cause of human tuberculosis, and the animal pathogens, M. bovis and M. orygis , causes of tuberculosis in a broad range of mammalian hosts, including humans. Since the late 1800s, M. tb and M. bovis have shown distinct differences in clinical presentation and virulence following experimental infection. However, the pathogenicity of M. orygis has yet to be subject to experimental investigation. Despite possessing the smallest genome of the three, M. orygis is hypervirulent in C57BL/6 mice, comparable to M. bovis , but markedly different from M. tb. Proteomic comparisons, gene disruptions and infection studies reinforced the importance of the canonical virulence factor, ESAT-6, and identified MPT70 as a non-canonical virulence factor. The demonstration of differential virulence among these MTBC lineages necessitates a reconsideration of M. tb as the default organism for pathogenesis studies and has fundamental and translational implications for tuberculosis research.
