Zhao Yuanjing, Xu Haoran, Wang Hui, Wang Ping, Chen Simin
State Key Laboratory of South Western Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
Mol Biomed. 2024 Nov 27;5(1):62. doi: 10.1186/s43556-024-00221-y.
Pseudomonas aeruginosa is a significant opportunistic pathogen, and its complex mechanisms of antibiotic resistance pose a challenge to modern medicine. This literature review explores the advancements made from 1979 to 2024 in understanding the regulatory networks of antibiotic resistance genes in Pseudomonas aeruginosa, with a particular focus on the molecular underpinnings of these resistance mechanisms. The review highlights four main pathways involved in drug resistance: reducing outer membrane permeability, enhancing active efflux systems, producing antibiotic-inactivating enzymes, and forming biofilms. These pathways are intricately regulated by a combination of genetic regulation, transcriptional regulators, two-component signal transduction, DNA methylation, and small RNA molecules. Through an in-depth analysis and synthesis of existing literature, we identify key regulatory elements mexT, ampR, and argR as potential targets for novel antimicrobial strategies. A profound understanding of the core control nodes of drug resistance offers a new perspective for therapeutic intervention, suggesting that modulating these elements could potentially reverse resistance and restore bacterial susceptibility to antibiotics. The review looks forward to future research directions, proposing the use of gene editing and systems biology to further understand resistance mechanisms and to develop effective antimicrobial strategies against Pseudomonas aeruginosa. This review is expected to provide innovative solutions to the problem of drug resistance in infectious diseases.
铜绿假单胞菌是一种重要的机会致病菌，其复杂的抗生素耐药机制给现代医学带来了挑战。本文献综述探讨了1979年至2024年在理解铜绿假单胞菌抗生素耐药基因调控网络方面取得的进展，特别关注这些耐药机制的分子基础。该综述强调了耐药涉及的四个主要途径：降低外膜通透性、增强主动外排系统、产生抗生素失活酶和形成生物膜。这些途径受到遗传调控、转录调节因子、双组分信号转导、DNA甲基化和小RNA分子等多种因素的复杂调控。通过对现有文献的深入分析和综合，我们确定关键调控元件mexT、ampR和argR为新型抗菌策略的潜在靶点。对耐药核心控制节点的深入理解为治疗干预提供了新的视角，表明调节这些元件可能逆转耐药性并恢复细菌对抗生素的敏感性。该综述展望了未来的研究方向，提出利用基因编辑和系统生物学进一步了解耐药机制，并开发针对铜绿假单胞菌的有效抗菌策略。本综述有望为传染病耐药问题提供创新解决方案。
