近日,来自诺丁汉大学的研究者对细菌的感染以及细菌间信号交流进行了深入的研究,研究者首次提出了降低细菌间信号传递交流的方法,细菌间的信号交流主要依赖于群体感性系统(quorum-sensing,QS),群体感性系统是一种依赖于细菌细胞数量的信号交流系统,研究者揭示了如何停止细菌间的交流来达到关闭细菌毒力产生的目的。
近年来,致病菌不断增加对传统抗生素的耐药性,包括诺丁汉大学的研究者在内的全世界的医药科学家正在奋起研究,试图去寻找到一种抵御致病菌感染的方法,本项研究中,研究者使用了一种群体感应淬灭的化合物来感染细菌间进行信号传递,从而感染细菌的生长,最终使得细菌致死。
细菌(铜绿假单胞菌)可以利用群体感应系统(QS)中的信号分子来进行相互交流以及基因表达的控制,同时铜绿假单胞菌也可以利用QS系统来引发一系列的感染,耐甲氧西林金黄色葡萄球菌也是如此,可以引发严重的感染性疾病。研究者Stephen Diggle表示,QS系统控制的因子只有在细胞密度达到一定程度时才会发挥出作用,而且QS系统也只有在细胞数量一定的时候才能够刺激细菌的某些行为,尤其是致病性。
这项研究刊登在了近日的国际杂志PNAS上,文章中,研究者提出,在铜绿假单胞菌中,细胞的密度是调节QS系统的关键因子,运用特殊的培养基以及分子操作技术,研究小组揭示了QS信号通路只是在低细胞密度的时候发生,但是对细菌并没有带来好处,然而在细胞密度高的时候,QS才会发挥巨大作用,对于细菌的感染非常有利。
未来,研究者的研究将致力于在感染者身上进行相关的实验研究,细菌可以利用QS系统来控制毒力基因的表达,进而控制毒力蛋白的产生,研究者将会解释,什么时候细菌会释放大量的毒素来引起人类的严重感染。这项研究同时也揭示了,控制感染性细菌的细胞密度(bacterial population density)对于避免毒性感染的重要性。(生物谷:T.Shen编译)
doi:10.1073/pnas.1118131109
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Density-dependent fitness benefits in quorum-sensing bacterial populations
Sophie E. Darcha, Stuart A. Westb, Klaus Winzera, and Stephen P. Digglea,1
It has been argued that bacteria communicate using small diffusible signal molecules to coordinate, among other things, the production of factors that are secreted outside of the cells in a process known as quorum sensing (QS). The underlying assumption made to explain QS is that the secretion of these extracellular factors is more beneficial at higher cell densities. However, this fundamental assumption has never been tested experimentally. Here, we directly test this by independently manipulating population density and the induction and response to the QS signal, using the opportunistic pathogen Pseudomonas aeruginosa as a model organism. We found that the benefit of QS was relatively greater at higher population densities, and that this was because of more efficient use of QS-dependent extracellular “public goods.” In contrast, the benefit of producing “private goods,” which are retained within the cell, does not vary with cell density. Overall, these results support the idea that QS is used to coordinate the switching on of social behaviors at high densities when such behaviors are more efficient and will provide the greatest benefit.