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群体感应淬灭:针对铜绿假单胞菌的药物发现方法。

Quorum Quenching: A Drug Discovery Approach Against Pseudomonas aeruginosa.

机构信息

Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur 784028, Assam, India.

Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Tezpur 784028, Assam, India.

出版信息

Microbiol Res. 2022 Nov;264:127173. doi: 10.1016/j.micres.2022.127173. Epub 2022 Aug 23.

Abstract

Pseudomonas aeruginosa, a ubiquitous opportunistic and nosocomial biofilm-forming pathogen with complex, interconnected and hierarchical nature of QS systems (Las, Rhl, PQS, and IQS), is posing the biggest challenge to the healthcare sector and have made current chemotherapies incapable. Conventional antibiotics designed to intercept the biochemical or physiological processes precisely of planktonic microorganisms exert extreme selective pressure and develop resistance against them thereby emphasizing the development of alternative therapeutic approaches. Additionally, quorum sensing induced pathogenic microbial biofilms and production of virulence factors have intensified the pathogenicity, drug resistance, recurrence of infections, hospital visits, morbidity, and mortality many-folds. In this regard, QS could be a potential druggable target and the discovery of QS inhibiting agents as an anti-virulent measure could serve as an alternative therapeutic approach to conventional antibiotics. Quorum quenching (QQ) is a preferred strategy to combat microbial infections since it attenuates the pathogenicity of microbes and enhances the microbial biofilm susceptibility to antibiotics, thus qualifying as a suitable target for drug discovery. This review discusses the QS-induced pathogenicity of P. aeruginosa, the hierarchical QS systems, and QS inhibition as a drug discovery approach to complement classical antibiotic strategy.

摘要

铜绿假单胞菌是一种普遍存在的机会性病原体,也是医院内生物膜形成的病原体,具有复杂、相互关联和分层的 QS 系统(Las、Rhl、PQS 和 IQS),这对医疗保健部门构成了最大的挑战,使当前的化疗药物无能为力。设计用于精确拦截浮游微生物生化或生理过程的传统抗生素会对其产生极端的选择性压力,并导致它们产生耐药性,从而强调了开发替代治疗方法的必要性。此外,群体感应诱导的致病性微生物生物膜和毒力因子的产生加剧了致病性、耐药性、感染复发、医院就诊、发病率和死亡率等方面的问题。在这方面,QS 可以成为一个潜在的可成药靶点,而发现 QS 抑制剂作为一种抗毒力措施,可以作为对抗生素的替代治疗方法。群体感应淬灭(QQ)是一种对抗微生物感染的首选策略,因为它可以降低微生物的致病性,并增强微生物生物膜对抗生素的敏感性,因此有资格成为药物发现的合适目标。本综述讨论了铜绿假单胞菌的 QS 诱导致病性、分层 QS 系统以及 QS 抑制作为一种药物发现方法,以补充经典抗生素策略。

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