Dr Baoxue Ge’s team reveals novel mechanism for Mycobacterium tuberculosis to suppresses immunity


Tuberculosis is a serious threat to public health in China and the world, but the pathogenesis of Mycobacterium tuberculosis(Mtb) is still unclear. On January 15 2020, Nature published the latest research titled " Host-mediated ubiquitination of a mycobacterial protein suppresses immunity " from the team of Prof. Baoxue Ge. They found that secreted protein Rv0222, an important virulence factor of Mtb, suppresses the host immune response by utilizing host ANAPC2 mediated K-11-linked ubiquitination. The function of the host E3 ligase ANAPC2 as a modifier of Rv0222 ubiquitination highlights the versatile mechanisms underlying the host-M. tuberculosis interactions, and research will expand to other host E3 ligases-mediated ubiquitination in the future. Besides, Rv0222 ubiquitination may represent an important strategy for Mtb to modulate host immune signaling pathways, paving the way for the development of effective anti-tuberculosis therapy by targeting the Rv0222/ANAPC2 interface.

This research work has been highly concerned and affirmed by the domestic and foreign experts. Professor Bennett h. Penn from University of California published Comment "an M. tuberculosis metallic enzyme moonlights as an anti-immunology effector" on Cell Host & microbe, saying “This approach identified Rv0222 as being able to suppress inflammation and their analyses suggest an intriguing model whereby Rv0222 acts as a bifunctional protein, with a metabolic role in the bacterial cytoplasm, yet also a role ‘‘moonlighting’’ as an effector in the host cytoplasm. This screening approach is powerful and could be readily coupled to a wide range of assays to probe the mechanisms by which in M. tuberculosis alters host cell physiology, providing insights that could one day be leveraged for therapeutic benefit.”. Recently, Professor Ouyang Songying from Fujian Normal University introduced this work in Research Highlight section from Science Bulletin journal and believed that “the discoveries could make ready for the improvement of viable antituberculosis drugs that focus on the Rv0222-ANAPC2 interface”.

This work was completed by research teams of Prof. Baoxue Ge from Tongji University and Prof. Zihe Rao from Shanghai Tech University which was supported by grants from the Chinese National Program on Key Basic Research Project, the National Natural Science Foundation of China, and the most important clinical discipline in Shanghai.