Research

Macao Polytechnic University research team discovers a new mechanism to regulate Pseudomonas aeruginosa metabolism and virulence

A research team from the Faculty of Applied Sciences of Macao Polytechnic University (MPU), Professor Liu Huanxiang, Lecturer Zhang Qianqian, and the Center for Infectious Diseases/National Key Laboratory of Biotherapy of West China Hospital of Sichuan University and Center for Infection of West China Hospital, have jointly published a journal article “Molecular mechanism of the one-component regulator RccR on bacterial metabolism and virulence” in the top journal of molecular biology--Nucleic Acids Research titled “Molecular mechanism of the one-component regulator RccR on bacterial metabolism and virulence”, revealing the molecular mechanism of the novel one-component system RccR in regulating carbon metabolism and virulence of Pseudomonas aeruginosa, which is of great significance as a guideline for the clinical treatment of persistent infections caused by Pseudomonas aeruginosa.

Nucleic Acids Research is an Oxford University Press journal focusing on biochemistry and molecular biology, with an impact factor of 14.9, ranking in the top 2% of molecular biology journals, and is a top journal in the field. Pseudomonas aeruginosa, a gram-negative bacterium, is a common opportunistic causative agent of hospital-acquired infections, with a high rate of clinical infections and lethality, and has been listed by the World Health Organization as one of the pathogens that urgently require the development of novel antibiotics. In the present study, we demonstrated for the first time that the P. aeruginosa carbon transcription factor RccR can directly regulate the expression of virulence-related genes mvaU and algU, and switch its DNA recognition pattern through conformational changes induced by the binding or release of 2-keto-3-deoxy-6-phosphogluconate (KDPG). In order to investigate the mechanism of KDPG-induced structural transition, the research team analyzed the crystal structure of the 2.0 Å RccR-KDPG complex and further simulated the structural changes of RccR in the presence and absence of KDPG by molecular dynamics simulation. The in vitro and in vivo experiments further confirmed that RccR can directly regulate the gene expression levels of mvaU and algU, and the regulatory activity increases with the concentration of KDPG. This study not only reveals the physiological function and molecular mechanism of RccR, but also lays the foundation for finding new targets for the treatment of Pseudomonas aeruginosa infections, which will open the door to scientific research for human health and contribute to the health industry in Macao.