Development of quorum-based anti-virulence therapeutics targeting Gram-negative bacterial pathogens.
Development of quorum-based anti-virulence therapeutics targeting Gram-negative bacterial pathogens.
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DOI：
10.3390/ijms140816570
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发表时间：
2013-08-09
影响因子：
5.6
通讯作者：
Yew WS
中科院分区：
文献类型：
--
作者：
Tay SB;Yew WS
群体感应是一种依赖于细胞密度的信号传导现象，被细菌用于协调群体范围内的表型，如毒力基因的表达、抗生素耐药性和生物膜的形成。最近，鉴于致病菌耐药性的增加，破坏细菌通讯已成为一种具有巨大治疗潜力的抗毒策略。群体猝灭治疗方法有望降低耐药性发展的风险，因为对毒力的干扰通常不会影响细菌的生长和适应性，因此不会对耐药菌株施加相关的选择压力。随着对细菌通讯网络和机制的深入了解，针对各种临床意义重大的细菌病原体，开发了许多群体猝灭方法。特别是革兰氏阴性菌是一组重要的病原体，因为它们共同导致了大多数医院获得性感染。在这里，我们讨论了目前对现有群体感应机制的理解，并提出了针对这组致病菌开发的重要抑制策略。
Quorum sensing is a cell density-dependent signaling phenomenon used by bacteria for coordination of population-wide phenotypes, such as expression of virulence genes, antibiotic resistance and biofilm formation. Lately, disruption of bacterial communication has emerged as an anti-virulence strategy with enormous therapeutic potential given the increasing incidences of drug resistance in pathogenic bacteria. The quorum quenching therapeutic approach promises a lower risk of resistance development, since interference with virulence generally does not affect the growth and fitness of the bacteria and, hence, does not exert an associated selection pressure for drug-resistant strains. With better understanding of bacterial communication networks and mechanisms, many quorum quenching methods have been developed against various clinically significant bacterial pathogens. In particular, Gram-negative bacteria are an important group of pathogens, because, collectively, they are responsible for the majority of hospital-acquired infections. Here, we discuss the current understanding of existing quorum sensing mechanisms and present important inhibitory strategies that have been developed against this group of pathogenic bacteria.
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