echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Active Ingredient News > Immunology News > ​EMBO Rep|Liu Cuihua/Qiu Xiaobo/Gao Fu team work together to reveal a new mechanism for Mycobacterium tuberculosis to escape host innate immunity

    ​EMBO Rep|Liu Cuihua/Qiu Xiaobo/Gao Fu team work together to reveal a new mechanism for Mycobacterium tuberculosis to escape host innate immunity

    • Last Update: 2021-05-22
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.
    tuberculosis, Mtb) infection is an important and fatal chronic infectious disease that seriously threatens global human health.

    According to the World Health Organization (WHO), there were about 10 million new TB patients worldwide in 2019, and about 1.
    41 million people died of TB.

    Mtb is a facultative intracellular parasite that can use a variety of strategies to interfere with the normal function of host cells to escape the host's immune response and achieve its long-term survival in host cells.

    Liu Cuihua's research group from the Institute of Microbiology, Chinese Academy of Sciences has long been committed to studying the molecular mechanisms of Mtb and other important pathogens interacting with the host, especially focusing on the molecular mechanism of Mtb's use of the host ubiquitin system to regulate the host's innate immune response.

    Mtb encodes a series of eukaryotic-like phosphatase/kinase family proteins, among which the eukaryotic-like tyrosine phosphatase PtpA and the eukaryotic-like serine/threonine protein kinase PknG are both secreted effector proteins, and are related to the intracellular survival of Mtb.
    The process is closely related, so PtpA and PknG have always been important targets for the development of new anti-tuberculosis drugs.

    In-depth study of the molecular mechanisms of PtpA and PknG interfering with host immune function will help provide new anti-tuberculosis targets based on the Mtb-host interaction interface, and provide new strategies for the development of new types of tuberculosis prevention and treatment drugs.

    Previous research by Liu Cuihua’s group found that Mtb PtpA interacts with host ubiquitin (Ub), and successively revealed the molecular mechanism of PtpA by capturing Ub in the cytoplasm to activate autophosphatase activity and thereby inhibit the host’s innate immune response (Nature Immunology, 2015).
    And the molecular mechanism that PtpA promotes tumor cell proliferation in a ubiquitin-independent form in the nucleus (Nature Communications, 2017).On May 2, 2021, the latest results of the collaboration between Liu Cuihua's research group, Professor Qiu Xiaobo's team from Beijing Normal University and the Gao Fu team of the Institute of Microbiology, were published in EMBO reports, entitled M.
    tuberculosis protein kinase G impairs host immunity by acting as an unusual ubiquitinating enzyme.

    This study found for the first time that Mtb PknG can specifically bind to a key protein of the host ubiquitin system, the ubiquitin coupling enzyme (E2) UbcH7.

    Moreover, PknG has both non-classical ubiquitin activating enzyme (E1) and ubiquitin ligase (E3) activities, and can use its various enzyme activities to target and regulate the host ubiquitin system, thereby inhibiting the host's innate immune response (Figure 1).

    In this paper, the researchers explored the regulation of the host's innate immunity by PknG, the key effector protein of Mtb, through a series of biochemical, cellular and mouse experiments, both in vitro and in vivo.

    Studies have found that PknG is secreted into host cells during Mtb infection, and binds to UbcH7 through its new Ubl (Ubiquitin-like) domain, and then exerts non-classical E1 and isopeptidase activities to promote the UbcH7-Ub complex.
    Formation and dissociation to obtain activated Ub; at the same time, PknG binds to tumor necrosis factor receptor-related factor 2 (TRAF2) and TGF-β activated kinase 1 (TAK1), and transfers the activated Ub to TRAF2 and TAK1, This mediates their ubiquitination and degradation, ultimately inhibits the activation of the NF-κB signaling pathway, and promotes the intracellular survival of Mtb (Figure 1).

    Figure 1.
    Mtb PknG uses its non-classical ubiquitinase activity to inhibit the host's innate immune response.
    In summary, this study clarifies a new mechanism for Mtb to suppress the host's innate immunity through its effector protein PknG, and also reveals a pathogen target A new strategy for the host ubiquitin system.
    This study also suggests that inhibitors based on PknG non-classical ubiquitinase activity are expected to be potential new drugs for the treatment of tuberculosis. It is reported that the project researcher Wang Jing of Liu Cuihua's research group, the doctoral student Ge Pupu and the master student Lei Zehui are the co-first authors of the paper.
    Researcher Liu Cuihua from the Institute of Microbiology of the Chinese Academy of Sciences, Professor Qiu Xiaobo from Beijing Normal University, and a senior from the Institute of Microbiology of the Chinese Academy of Sciences Academician Fu is the co-corresponding author of this article.

    Original link: Plate maker: Notice for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article, personal forwarding and sharing are welcome, and it is prohibited without permission Reprinted, the author has all legal rights, offenders must be investigated.

    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.