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Volume 46 Issue 12
Dec.  2019
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Article Contents

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

doi: 10.1016/j.jgg.2019.12.002
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  • Corresponding author: E-mail address: hezhengguo2019@163.com (Zheng-Guo He)
  • Received Date: 2019-11-05
  • Accepted Date: 2019-12-02
  • Rev Recd Date: 2019-11-28
  • Available Online: 2019-12-28
  • Publish Date: 2019-12-20
  • 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.
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