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[群体感应基因表达——对抗细菌致病性的潜在药物靶点]

[Quorum sensing of genes expression--perspective drug target against bacterial pathogenicity].

作者信息

Khmel' I A, Metlitskaia A Z

出版信息

Mol Biol (Mosk). 2006 Mar-Apr;40(2):195-210.

Abstract

Bacteria are capable to sense an increase of cell density population and to reply quickly and coordinately by the induction of special sets of genes. This type of the regulation was named Quorum Sensing (QS); it is based on the effect of low-molecular-weight signaling molecules of different nature (autoinducers) which accumulate in the culture at high density of bacterial population and interact with receptor regulatory proteins. QS systems are the global regulators of bacterial genes expression and play a key role in the control of many metabolic processes in cell including the regulation of virulence of bacteria. Here we review the molecular mechanisms of QS systems functioning in bacteria belonging to different taxonomic groups and discuss the potential of QS regulation as a new drug target for the treatment of bacterial infections. At present this approach is accounted as a new alternative strategy of antimicrobial therapy directed on the development of drugs inhibiting QS regulation and active just against pathogenicity of bacteria (antipathogenic drugs). Such a strategy allows to avoid a wide dissemination of resistant forms of pathogenic bacteria and the formation of biofilms increasing in many times the resistance of bacteria to drug preparations.

摘要

细菌能够感知细胞群体密度的增加,并通过诱导特定的基因集快速且协调地做出反应。这种调节类型被称为群体感应(QS);它基于不同性质的低分子量信号分子(自诱导物)的作用,这些分子在细菌群体高密度培养时积累,并与受体调节蛋白相互作用。群体感应系统是细菌基因表达的全局调节因子,在控制细胞内许多代谢过程中发挥关键作用,包括细菌毒力的调节。在这里,我们综述了不同分类群细菌中群体感应系统发挥作用的分子机制,并讨论了群体感应调节作为治疗细菌感染新药物靶点的潜力。目前,这种方法被视为抗菌治疗的一种新的替代策略,旨在开发抑制群体感应调节且仅针对细菌致病性起作用的药物(抗致病性药物)。这样的策略能够避免致病性细菌耐药形式的广泛传播以及生物膜的形成,生物膜会使细菌对药物制剂的耐药性增加数倍。

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