Recently, Professor Li Weihui's team from the School of Life Science and Technology of Guangxi University published an online paper entitled "Lsr2 acts as a cyclic di-GMP receptor that promotes keto-mycolic acid synthesis and biofilm formation in mycobacteria" in the Nature sub-journal Nature Communications, as the team discovered a new second messenger receptor Lsr2, revealed that c-di-GMP promotes the synthesis of mycobacterial acid, and thus a new molecular mechanism regulates the formation of bacterial biofilms. The first author of the paper is Ling Xiaocui, a doctoral student in the School of Life Science and Technology, and the corresponding author is Li Weihui, a professor in the same school and from State Key laboratory for Conservation and Utilization of Subtropical Agro- Bioresources. The research was supported by the National Key Research and Development Program, the National Natural Science Foundation and the Guangxi Outstanding Youth Science Foundation, and was supervised by Professor He Zhengguo of GXU.
Tuberculosis (TB) is a zoonotic infectious disease caused by Mycobacterium tuberculosis (Mtb) complex group. It is the number one killer of single infectious diseases and has been a major global health concern. In recent years, with the emergence of multi-drug resistant mycobacterium tuberculosis, the prevention and control of tuberculosis has encountered unprecedented difficulties and challenges. Bacterial biofilm is an important physical barrier against external environmental stress, which can greatly improve the multidrug resistance of bacteria. C-di-GMP is a common second messenger and "star molecule" in bacteria, which regulates many physiological processes such as bacterial biofilm formation through receptors. However, the molecular mechanism by which the signaling molecule c-di-GMP regulates the formation of mycobacterium biofilms is still unclear, and the relevant receptors have not yet been discovered.
The team found that Lsr2 acts as a new receptor for the second messenger c-di-GMP, binding specifically in a 1:1 ratio. In addition, Lsr2 promotes the formation of bacterial biofilm by positively regulating the expression of (3R) -hydroxyacyl-ACP dehydratase (HadD), which mediates the synthesis of Keto-mycolic acid, a major component of mycobacterium cell wall. In addition, c-di-GMP can be used as an activator of Lsr2 to enhance the positive regulatory effect of Lsr2 on HadD. The above results will provide strategies for inhibiting multi-drug resistance of Mycobacterium tuberculosis by blocking cell wall lipid synthesis, and further provide theoretical basis for discovering new drug targets and developing novel vaccines against tuberculosis.
