MpbR, an essential transcriptional factor for Mycobacterium tuberculosis survival in the host, modulates PIM biosynthesis and reduces innate immune responses

Yugang Li^a,
Weihui Li^b,
Zhiwei Xie^a,
Hui Xu^a,
Zheng-Guo He^{a, b
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a.
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
b.
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning, 530004, China

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Corresponding author: E-mail address: hezhengguo2019@163.com (Zheng-Guo He)

摘要

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Abstract: Mycobacterium tuberculosis possesses unique cellular envelope components that contribute to bacterial escape from host immune surveillance. Phosphatidylinositol mannosides (PIMs) and their higher derivatives are important molecules implicated in host-pathogen interactions in the course of tuberculosis. However, the biosynthetic regulation of these specific lipids and its effect on the bacterial fate in the infected host remain unclear. Here, we show that a hypothetical M. tuberculosis transcriptional factor designated as MpbR negatively regulates two transporter genes and affects mycobacterial PIM biosynthesis and biofilm formation. MpbR inhibits the accumulation of acylated PIM lipids and triggers the mycobacterium to reduce the production of reactive oxygen species and NO during infection, which enhances the survival ofM. tuberculosis in macrophages. MpbR deletion reduces M. tuberculosis lung burdens and inflammation of infected mice. These findings provide new insights into the regulation of mycobacterial lipid metabolism and its correlation with pathogenesis of M. tuberculosis.
- Transcriptional factor /
- Lipid metabolism

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参考文献(54)

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