Quorum sensing: an emerging target for antibacterial chemotherapy?
Quorum sensing: an emerging target for antibacterial chemotherapy?
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DOI：
10.1517/14728222.6.3.257
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发表时间：
2002-06-01
影响因子：
5.8
通讯作者：
Williams, Paul
中科院分区：
文献类型：
--
作者：
Williams, Paul
对多种抗生素类别表现出耐药性的细菌菌株的出现对医学和公共卫生构成了重大威胁。在过去的几十年里，由于药物发现计划未能提供具有新作用模式的新广谱抗菌药物，这一问题更加复杂。因此，人们对通过减弱毒力来破坏病原菌引起感染的能力的抗菌靶标重新产生了兴趣。在这方面，几乎所有细菌感染的一个关键特征是病原体必须达到足以压倒宿主防御的临界细胞群体密度。现在已知许多病原体通过细胞间通讯以细胞密度依赖性方式调节多种生理过程，包括毒力。这种现象依赖于可扩散信号分子与传感器激酶或反应调节剂的相互作用，已被称为“群体感应”。这篇综述考虑了群体感应的分子基础，以及它是否构成了一个潜在的治疗目标，设计的小分子拮抗剂能够控制感染，通过衰减适应宿主环境。
The emergence of bacterial strains exhibiting resistance to multiple antibiotic classes poses a major threat to medicine and public health. This has been compounded over the last few decades by the failure of drug discovery programmes to provide new broad spectrum antibacterials with novel modes of action. As a consequence, there is renewed interest in antibacterial targets which disrupt the capacity of pathogenic bacteria to cause infection by attenuating virulence. In this respect, one crucial feature of almost all bacterial infections is that the pathogen must attain a critical cell population density sufficient to overwhelm the host defences. Many pathogens are now known to regulate diverse physiological processes, including virulence, in a cell density dependent manner through cell-cell communication. This phenomenon, which relies upon the interaction of a diffusible signal molecule with a sensor kinase or response regulator, has become known as 'quorum sensing'. This review considers the molecular basis of quorum sensing and whether it constitutes a potential therapeutic target for the design of small molecule antagonists capable of controlling infection by attenuating adaptation to the host environment.