Virulence attenuating combination therapy: a potential multi-target synergy approach to treat Pseudomonas aeruginosa infections in cystic fibrosis patients,RSC Medicinal Chemistry

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Virulence attenuating combination therapy: a potential multi-target synergy approach to treat Pseudomonas aeruginosa infections in cystic fibrosis patients
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-02-19 , DOI: 10.1039/c9md00566h
Elana Shaw ₁ , William M Wuest _{1,

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Affiliation

The World Health Organization considers the discovery of new treatments for P. aeruginosa a top priority. Virulence attenuating combination therapy (VACT) is a pragmatic strategy to improve bacterial clearance, repurpose outmoded antibiotics, improve drug efficacy at lower doses, and reduce the evolution of resistance. In vitro and in vivo studies have shown that adding a quorum sensing inhibitor or an extracellular polymeric substance repressor to classical antibiotics synergistically improves antipseudomonal activity. This review highlights why VACT could specifically benefit cystic fibrosis patients harboring chronic P. aeruginosa infections, outlines the current landscape of synergistic combinations between virulence-targeting small-molecules and anti-pseudomonal drugs, and suggests future directions for VACT research.

中文翻译：

毒力减弱联合疗法：治疗囊性纤维化患者铜绿假单胞菌感染的潜在多靶点协同方法

世界卫生组织认为发现铜绿假单胞菌新疗法是当务之急。毒力减弱联合疗法（VACT）是一种务实的策略，旨在提高细菌清除率，重新利用过时的抗生素，提高较低剂量的药物疗效，并减少耐药性的演变。体外和体内研究表明，在经典抗生素中添加群体感应抑制剂或细胞外聚合物阻遏剂可协同提高抗假单胞菌活性。这篇综述强调了为什么 VACT 可以特别有利于慢性铜绿假单胞菌感染的囊性纤维化患者，概述了毒力靶向小分子和抗假单胞菌药物之间协同组合的现状，并提出了 VACT 研究的未来方向。

更新日期：2020-02-19

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