Scientists have come up with new ideas for the development of anti-tuberculosis drugs

Recently, Liu Cuihua of the Institute of Microbiology of the Chinese Academy of Sciences discovered a new mechanism for TB mycobacteria (Mtb) to regulate host cell function by secreting a series of effect proteins to escape the host's inherent immune clearance, and revealed the dynamic process and molecular mechanism of the game between pathogens and hosts, providing new ideas and special targets for anti-tuberculosis drug research and development. The results were recently published
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TB caused by Mtb is an ancient chronic infectious disease and is still the single deadliest infectious disease in the world. Mtb is an endocytopathic bacteria that secretes a variety of effect proteins into the host cell, which interferes with cell signaling pathology and biological function, ultimately promoting the survival of the pathogen in the host cell and leading to host cell lesions.
recent years, a growing body of research has shown that chronic inflammation caused by infections of pathogenic microorganisms, including multiple viruses and bacteria, increases the risk of tumor development. However, the correlation between chronic infection caused by Mtb and lung cancer has not been determined, and little is known about the molecular regulatory mechanism of Mtb effect protein in tumor development.
recently, the team found that the Mtb-effect protein PtpA, a somatic tyrosine phosphatase, not only regulates the inherent immune signaling pathline in the host cytoplasm, but also enters the host cell nucleus. ChIP-seq analysis results suggest that PtpA regulates the expression of a series of host genes in the host cell nucleus, mainly related to immune regulation and biological functions such as cell proliferation and migration.
Further studies have found that PtpA can be directly integrated into the initiator region of the GADD45A gene and inhibits the transcription of the gene, which in turn promotes the proliferation and migration of A549 cells of human non-small cell lung cancer and its tumor-forming ability in naked mice, and that the regulatory function relies on PtpA's DNA binding ability without relying on its phosphatase activity. In addition, potential target genes in the nuclei of PtpA-regulated host cells include certain non-coding RNA genes that are closely related to tumor development.
The study found the first Mtb-effect protein PtpA that enters the host cell nucleus to regulate host immunity and cell proliferation, revealing the molecular mechanisms by which Mtb can promote the development of lung cancer under certain circumstances through secreted effect proteins
(Source: ScienceDaily)