Research Progress in Identifying PqsR Antagonists for Treating Pseudomonas Aeruginosa Infection
DOI:
https://doi.org/10.53469/jcmp.2024.06(11).11Keywords:
Pseudomonas aeruginosa, Drug resistance, PQSR, Quorum sensing, AntagonistsAbstract
Pseudomonas aeruginosa (PA), a gram-negative bacterium, is a major pathogen responsible for serioussevere infections in immunocompromised individuals and patients with cystic fibrosis. It causes nosocomial (medically related) healthcare-associated) infections and is known for its resistance to antibiotics resistance. PA utilizes complex quorum sensing networks to regulate the production of virulence factors and the development of biofilm, thus contributing to its multidrug resistance. The bacterium uses employs three interconnected quorum sensing systems: the las and rhl systems, which use N-acyl homoserine lactones, and the pqs system, which is based relies on alkyl quinols. A major focus of current research is on the transcriptional regulator PqsR (also known as the multiple virulence factor regulator or MvfR), a key protein in the quorum sensing system. This review examines recent advances in combating PA infections by disrupting these quorum sensing networks. We describe the potential of targeting these networks to reduce virulence and resistance, with a specific focus on PqsR antagonists. These antagonists disrupt the cell-cell communication that the bacteria rely on to produce virulence factors, thereby limiting and potentially eliminating multidrug-resistant infections. We evaluate both natural and synthetic PqsR inhibitors, providing a detailed description of their mechanisms and efficacy. In addition, the review discusses drug repurposing, highlighting various approved compounds that may modulate the quorum sensing system of PA. Through molecular docking studies and in vitro assays, several compounds were identified as potential candidates for further development. In conclusion, the review provides directions for future research to identify novel, safe, and effective natural products to inhibit infections caused by this pathogen.
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Copyright (c) 2024 Tiantian Shen, Wei Zhang, Guoxu Wang, Yihai Gu
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