New findings help to improve the development of anti-TB drugs

Tuberculosis (TB) caused by M. tuberculosis (Mtb) remains to be a major global public health challenge. TB research and new drug development are urgently needed due to the limited availability of drugs that are currently available to treat TB, especially MDR-TB and XDR-TB. Mtb is a typical intracellular pathogen. Mtb evolved a variety of immune escape strategies in the process of long-term coexistence and interaction with the host. Therefore, in-depth study of the interaction between Mtb and the host immune system using recombinant human proteins and its regulatory mechanism is of great significance for elucidating the molecular mechanism of Mtb latent infection and pathogenesis and providing new drug targets for the development of anti-TB drugs.

Liu Cuihua research group at The Institute of Microbiology has been working on the molecular mechanism of the interaction between Mtb and other important pathogens and hosts. In recent years, he has published a series of studies in Nature Immunology (2015), The Journal of Immunology (2015), etc., to uncover the new mechanism of Mtb regulating host cell function then escaping host innate immunity through secreting effect protein (including PtpA and Mce3E, etc.). In addition to investigating the role of effector proteins in the immune regulation of the host from the perspective of pathogens, the team explored the mechanisms of immune defense in pathogen infection from a host perspective. In the process of in-depth study of the regulatory function of the Mtb-effector protein PtpA, they identified host interaction protein TRIM27 (an ubiquitin ligase) of PtpA.

Further studies have shown that TRIM27 can act as a host restriction factor to inhibit the survival of mycobacteria in macrophages. TRIM27 can activate JNK / p38 signaling pathway of host cells and promotes apoptosis in ubiquitin ligase-dependent manner, thus inhibiting the intracellular survival of mycobacterium. Interestingly, the study also found that Mtb PtpA can bind to RING domain of TRIM27 protein to antagonise TRIM27-mediated activation process of innate immune signaling pathways and apoptosis in order to achieve the purpose of promoting intracellular survival of Mycobacterium. The study revealed the dynamic process and molecular mechanism of the interaction between pathogen and host, providing new ideas and specific targets for the development of antituberculosis drugs. Flarebio offers recombinant proteins of good quality such as recombinant ACSL3.