Scientists propose new ideas for anti-tuberculosis drug research and development
Scientists propose new ideas for anti-tuberculosis drug research and development
August 18, 2017 Source: Chinese Journal of Science
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Recently, Liu Cuihua, a researcher at the Institute of Microbiology, Chinese Academy of Sciences, discovered a new mechanism by which Mycobacterium tuberculosis (Mtb) evades the innate immune clearance of host by secreting a series of effector proteins to regulate host cell function, and reveals the dynamic process of mutual game between pathogens and hosts. And molecular mechanisms provide new ideas and specific targets for the development of anti-tuberculosis drugs. Related results were recently published in Nature Communication.
Tuberculosis caused by Mtb is an ancient chronic infectious disease and is still the single most infectious disease in the world. Mtb is an intracellular pathogen that secretes a variety of effector proteins into host cells, thereby interfering with cellular signaling pathways and biological functions, ultimately promoting the survival of pathogenic bacteria in host cells and leading to host cell pathology.
In recent years, more and more studies have shown that chronic inflammation caused by infection by pathogenic microorganisms (including a variety of viruses and bacteria) can increase the risk of tumor development. However, the correlation between chronic infection caused by Mtb and lung cancer is still inconclusive. The molecular regulation mechanism of Mtb effector protein in tumor development is still poorly understood.
Recently, the team found that the Mtb effector protein PtpA, a eukaryotic tyrosine phosphatase, not only regulates the innate immune signaling pathway in the host cytoplasm but also enters the host nucleus. The results of ChIP-seq analysis indicated that PtpA can regulate the expression of a series of host genes in the host cell nucleus. These genes mainly involve immune regulation and biological functions such as cell proliferation and migration.
Further studies revealed that PtpA can directly bind to the promoter region of GADD45A gene and inhibit the transcription of this gene, and further promote the proliferation and migration ability of human non-small cell lung cancer A549 cells and its tumorigenic ability in nude mice, and this regulation The function depends on the DNA binding ability of PtpA and does not depend on its phosphatase activity. In addition, potential target genes in the host cell nucleus regulated by PtpA also include certain non-coding RNA genes closely related to tumorigenesis.
The study found that the first Mtb effector protein PtpA, which can enter the host cell nucleus to regulate host immunity and cell proliferation, reveals the molecular mechanism by which Mtb can promote the development of lung cancer through specific effector proteins. (KeXun)
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