Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is one of the most dangerous infectious pathogens worldwide. According to a World Health Organization report, more than 9 million people were estimated as new TB cases and about 1.5 million died from the disease in 2014. About half of the patients with multidrug-resistant tuberculosis were not successfully treated globally. Thus, there is an urgency to indentify new therapeutic targets for developing drugs that are available for drug-resistant tuberculosis treatment.

Dr. LIU Cuihua’s group at the Institute of Microbiology, Chinese Academy of Sciences has been investigating the molecular mechanisms underlying pathogen-host interactions. In 2015, her group published a series of papers, which revealed novel mechanisms involved in the regulation of host innate immunity by Mtb effector proteins, such as PtpA and Mce3E (Nature Immunology, 2015; The Journal of Immunology, 2015)

Dr. Liu’s group reported a new study on the host restriction factor during mycobacterial infection. They found that TRIM27, an E3 ubiquitin ligase in host cells, restricts the intracellular survival of mycobacteria, suggesting that it is a potential host restriction factor for Mtb. Moreover, they showed that TRIM27 suppresses the intracellular survival of mycobacteria by enhancing host immune-inflammatory responses mediated by JNK/p38 pathways as well as cell apoptosis.

Interestingly, Mtb PtpA antagonizes TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis through competitively binding to the RING domain of TRIM27.

Their findings highlighted an evolutionary dynamics of interactions between a host restriction factor and its pathogen antagonist during mycobacterial infection.

The paper entitled “The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection” has been published online in Scientific Reports with Dr. WANG Jing as the first author and Dr. LIU as the corresponding author. (http://www.nature.com/articles/srep34827).

The work was supported by grants from National Basic Research Programs of China, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the Youth Innovation Promotion Association CAS and Strategic Research Theme Fund and the University of Hong Kong.

Figure 1.Identification of TRIM27 as aMycobacterium tuberculosis(Mtb) PtpA-interacting host protein