Dong Y-h, Wang L-y, Zhang L-H
Institue of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Republic of Singapore
Philos Trans R Soc Lond B Biol Sci. 2007 Jul 29;362(1483):1201-11. doi: 10.1098/rstb.2007.2045.
The discovery of antibiotics early in the past century marked the beginning of active control and prevention of infectious microbial diseases. However, extensive use of antibiotics has also unavoidably resulted in the emergence of ‘superbugs’ that resist conventional antibiotics. The finding that many pathogens rely on cell-to-cell communication mechanisms, known as quorum sensing, to synchronize microbial activities essential for infection and survival in the host suggests a promising disease control strategy, i.e. quenching microbial quorum sensing or in short, quorum quenching. Work over the past few years has demonstrated that quorum-quenching mechanisms are widely conserved in many prokaryotic and eukaryotic organisms. These naturally occurring quorum-quenching mechanisms appear to play important roles in microbe–microbe and pathogen–host interactions and have been used, or served as lead compounds, in developing and formulating a new generation of antimicrobials. Characterization of the crystal structures of several types of quorum-quenching enzymes has provided valuable information to elucidate the catalytic mechanisms, as well as clues for future protein tailoring and molecular improvement. The discovery of quorum-sensing signal degradation enzymes in mammalian species represents a new milestone in quorum sensing and quorum quenching research. The finding highlights the importance of investigating their roles in host innate defence against infectious diseases and to determine the factors influencing their concentrations and catalytic activities.
上世纪早期抗生素的发现标志着积极控制和预防传染性微生物疾病的开端。然而,抗生素的广泛使用也不可避免地导致了对传统抗生素具有抗性的“超级细菌”的出现。许多病原体依赖细胞间通讯机制(即群体感应)来同步在宿主体内感染和生存所必需的微生物活动,这一发现提示了一种很有前景的疾病控制策略,即抑制微生物群体感应,简而言之就是群体淬灭。过去几年的研究表明,群体淬灭机制在许多原核生物和真核生物中广泛存在。这些天然存在的群体淬灭机制似乎在微生物-微生物以及病原体-宿主相互作用中发挥重要作用,并且已被用于或作为先导化合物来开发和配制新一代抗菌剂。几种群体淬灭酶晶体结构的表征为阐明催化机制提供了有价值的信息,也为未来蛋白质改造和分子改良提供了线索。在哺乳动物物种中发现群体感应信号降解酶代表了群体感应和群体淬灭研究中的一个新里程碑。这一发现凸显了研究它们在宿主抵御传染病的固有防御中的作用以及确定影响其浓度和催化活性的因素的重要性。