How does mycobacteria cause tuberculosis? The research team of Prof. GE Baoxue of Shanghai Pulmonary Hospital Affiliated to Tongji University, together with RAO Zihe academician of Shanghai University of Science and Technology Institute of Immunochemistry, had new findings. The "smart" protein secreted by tuberculosis bacteria can cause tuberculosis by luring human proteins to attack body’s immune system. At 2 a.m. on January 16, Beijing time (18 a.m. on January 15, London time), the world's top academic journal Nature published this important research online.

The study titled "Host-mediated ubiquitination of a mycobacterial protein suppresses immunity" found that the tuberculosis bacteria could secrete virulence factor Rv0222 when they infect human body，which can disguise itself through secondary processing with the help of human protein modification system to effectively withstand the attack of immune system. Shortly, the protein slyly took advantage of the body's "spear" (protein molecule) to attack its own "shield" (immune system), escaping from being attacked.

Prof. ZHAO Guoping, an academician of Chinese Academy of Sciences, and Prof. XIAO Heping, former chairman of Chinese Medical Association Tuberculosis Branch and chief clinical consultant of tuberculosis of Shanghai Pulmonary Hospital, said this work fully explained escape mechanism of tuberculosis, using ubiquitination to prevent immune attack, and moreover it broadened our vision about the function of protein modification system in infectious diseases. Further, through structural analysis and functional exploration, the researchers accurately pointed out that Rv0222 protein experienced K-11 ubiquitination on lysine at position 76 could exert virulence on human body, providing more precise targets for the development of new type anti-tuberculosis drugs in subsequent studies.

Prof. GE introduced that tuberculosis is still one of the leading causes of infection deaths worldwide. According to World Health Organization, more than 10 million new cases were reported worldwide in 2018 and widespread use of anti-tuberculosis drugs has led to drug resistance. So far, unknowable comprehensive pathogenesis and resistance mechanism, less rapid and accurate diagnosis, and lacking of new drugs still impede the prevention and treatment of tuberculosis. With the support of Science and Technology Ministry and National Natural Science Fund, researchers exploring the structure, function, and regulatory mechanism of key pathogens and host molecular machines in the process of tuberculosis infection, and development of new anti-TB drugs have been conducted on the basis of the theory that the interaction between tuberculosis and host lays the ground for infectious disease.

A series of important results have been published in international journals such as Nature, Nature Microbiology, Nature Communications, etc. as corresponding author, including 18 papers and 13 invention patents (5 authorized patents). Some team members became the owners of the National Young Talent Fund of China and the German Max Planck Scholarship for Postdoctoral Fellows and Shanghai Sun Program.

Dr. WANG Lin from Affiliated Shanghai Pulmonary Hospital, Master student WU Juehui from Tongji University School of Medicine, and LI Jun, associate researcher from Shanghai University of Science and Technology Institute of Immunochemistry are the co-first authors, Academician RAO Zihe and Prof. GE Baoxue as co-corresponding authors.