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了解铜绿假单胞菌耐药性的获得及其在缓解其发病机制方面可能的药理学方法。

Understanding resistance acquisition by Pseudomonas aeruginosa and possible pharmacological approaches in palliating its pathogenesis.

机构信息

Department of Microbiology, Central University of Haryana, Mahendergarh, Haryana 123031, India.

Department of Biotechnology, Central University of Haryana, Mahendergarh, Haryana 123031, India.

出版信息

Biochem Pharmacol. 2023 Sep;215:115689. doi: 10.1016/j.bcp.2023.115689. Epub 2023 Jul 20.

Abstract

Pseudomonas aeruginosa can utilize various virulence factors necessary for host infection and persistence. These virulence factors include pyocyanin, proteases, exotoxins, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), phospholipases, and siderophores that enable the bacteria to cause severe infections in immunocompromised individuals. P. aeruginosa falls into the category of nosocomial pathogens that are typically resistant to available antibiotics and therapeutic approaches. P. aeruginosa bio-film formation is a major concern in hospitals because it can cause chronic infection and increase the risk of mortality. Therefore, the development of new strategies to disrupt biofilm formation and improve antibiotic efficacy for the treatment of P. aeruginosa infections is crucial. Anti-biofilm and anti-quorum sensing (QS) activity can be viewed as an anti-virulence approach to control the infectious nature of P. aeruginosa. Inhibition of QS and biofilm formation can be achieved through pharmacological approaches such as phytochemicals and essential oils, which have shown promising results in laboratory studies. A regulatory protein called LasR plays a key role in QS signaling to coordinate gene expression. Designing an antagonist molecule that mimics the natural autoinducer might be the best approach for LasR inhibition. Here we reviewed the mechanism behind antibiotic resistance and alternative approaches to combat the pathogenicity of P. aeruginosa.

摘要

铜绿假单胞菌可以利用各种毒力因子来进行宿主感染和持续感染。这些毒力因子包括绿脓菌素、蛋白酶、外毒素、2-庚基-4-羟基喹啉 N-氧化物(HQNO)、磷脂酶和铁载体,使细菌能够在免疫功能低下的个体中引起严重感染。铜绿假单胞菌属于医院获得性病原体,通常对现有抗生素和治疗方法具有耐药性。铜绿假单胞菌生物膜的形成是医院的一个主要关注点,因为它会导致慢性感染并增加死亡率。因此,开发新的策略来破坏生物膜的形成并提高抗生素治疗铜绿假单胞菌感染的疗效至关重要。抗生物膜和抗群体感应(QS)活性可以被视为一种控制铜绿假单胞菌感染性的抗毒力方法。通过植物化学物质和精油等药理学方法可以抑制 QS 和生物膜的形成,这些方法在实验室研究中显示出了有希望的结果。一种叫做 LasR 的调节蛋白在 QS 信号传导中起着关键作用,以协调基因表达。设计一种模拟天然自体诱导物的拮抗剂分子可能是抑制 LasR 的最佳方法。在这里,我们回顾了抗生素耐药性的机制以及对抗铜绿假单胞菌致病性的替代方法。

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