Kaufmann Gunnar F, Park Junguk, Janda Kim D
Skaggs Institute for Chemical Biology, Department of Chemistry and Immunology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Expert Opin Biol Ther. 2008 Jun;8(6):719-24. doi: 10.1517/14712598.8.6.719.
Cell-to-cell communication via exchange of small molecules, 'autoinducers', is a widespread phenomenon among Gram-negative and -positive bacteria. This intercellular signaling that synchronizes population-wide gene expression in a cell-density-dependent manner is termed 'quorum sensing' (QS). The discovery that Gram-negative bacteria employ non-peptide structures, N-acyl homoserine lactones, to globally regulate production of secondary metabolites and proteins, initiated a new area of research. Subsequently, other quorum-sensing systems and small signaling molecules were identified. With the emergence of antibiotic-resistant bacteria, most prominently methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, new approaches for combating infections are needed. Inhibition of QS results in attenuation of virulence rather than direct killing of microbes.
We highlight current trends in preventing bacterial infections using quorum-quenching strategies.
We mainly focus on P. aeruginosa and S. aureus and their QS systems as targets for intervention.
RESULTS/CONCLUSION: New research strongly suggests that QS systems represent attractive targets for discovery of novel anti-infective agents, including immunotherapeutic strategies.
通过小分子“自诱导物”的交换进行细胞间通讯，在革兰氏阴性菌和革兰氏阳性菌中是一种普遍现象。这种以细胞密度依赖性方式同步全群体基因表达的细胞间信号传导被称为“群体感应”（QS）。革兰氏阴性菌利用非肽结构N-酰基高丝氨酸内酯来全局调节次级代谢产物和蛋白质的产生这一发现，开启了一个新的研究领域。随后，又鉴定出了其他群体感应系统和小信号分子。随着抗生素耐药菌的出现，最突出的是耐甲氧西林金黄色葡萄球菌（MRSA）和铜绿假单胞菌，需要新的抗感染方法。抑制群体感应会导致毒力减弱，而不是直接杀死微生物。
我们重点介绍使用群体猝灭策略预防细菌感染的当前趋势。
我们主要关注铜绿假单胞菌和金黄色葡萄球菌及其群体感应系统作为干预靶点。
结果/结论：新的研究有力地表明，群体感应系统是发现新型抗感染药物（包括免疫治疗策略）的有吸引力的靶点。
