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 of M. 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.

结核分枝杆菌具有独特的细胞包膜成分，有助于细菌从宿主免疫监视中逃逸。磷脂酰肌醇甘露糖苷（PIMs）及其高级衍生物是在结核病过程中与宿主-病原体相互作用有关的重要分子。但是，这些特定脂质的生物合成调控及其对感染宿主细菌命运的影响仍不清楚。在这里，我们显示了一个假想的结核分枝杆菌被称为MpbR的转录因子负调控两个转运蛋白基因，并影响分枝杆菌PIM的生物合成和生物膜形成。MpbR抑制酰化的PIM脂质的积累，并触发分枝杆菌减少感染过程中活性氧和NO的产生，从而提高巨噬细胞中结核分枝杆菌的存活率。MpbR缺失减少了结核分枝杆菌的肺负担和感染小鼠的炎症。这些发现提供了新的见解分枝杆菌脂质代谢的调控以及与发病相关性结核分枝杆菌。