Private link between signal and response in Bacillus subtilis quorum sensing

Private link between signal and response in Bacillus subtilis quorum sensing
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DOI:
10.1073/pnas.1316283111
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发表时间:
2014-01-28
影响因子:
11.1
通讯作者:
Mandic-Mulec, Ines
Mandic-Mulec, Ines
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Oslizlo, Anna;Stefanic, Polonca;Mandic-Mulec, Ines

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细菌利用群体感应(quorum sensing,QS)来协调它们的行为,细胞借此分泌可扩散的信号,产生与群体生活相关的表型反应。QS的典型模型是细胞外信号传导,其中信号分子与同源受体结合并引起许多细胞的协调反应。在这里,我们研究了QS输入(信号)和QS输出(响应)之间的联系,在ComQXPA QS系统的枯草芽孢杆菌通过表征comQ无效突变体的表型和健身。这些细胞缺乏产生ComX信号的酶,并且不会激活其他细胞中的ComQXPA QS系统。然而,除了信号的激活作用外,我们还发现了信号产生对QS系统的第二种抑制作用的证据。与激活不同,它可以影响其他细胞,抑制作用是私下的:在comQ细胞中QS的去抑制是细胞内的,只影响缺乏ComQ的突变细胞。因此,QS信号突变体具有过度响应的QS系统,并且在信号存在下过度产生次级代谢物表面活性素。这种表面活性素的过度生产与强大的健身成本有关,因为资源从初级代谢中转移。因此,作为一个私人的QS阻遏物,ComQ可能会受到保护,免受功能丧失突变的进化竞争。此外,我们发现,表面活性素参与社会选择机制,目标信号无效突变体与信号生产商共培养。我们的研究表明,通过多效性结合细胞内和细胞外信号,细菌可以产生进化稳定的QS系统。
Bacteria coordinate their behavior using quorum sensing (QS), whereby cells secrete diffusible signals that generate phenotypic responses associated with group living. The canonical model of QS is one of extracellular signaling, where signal molecules bind to cognate receptors and cause a coordinated response across many cells. Here we study the link between QS input (signaling) and QS output (response) in the ComQXPA QS system of Bacillus subtilis by characterizing the phenotype and fitness of comQ null mutants. These lack the enzyme to produce the ComX signal and do not activate the ComQXPA QS system in other cells. In addition to the activation effect of the signal, however, we find evidence of a second, repressive effect of signal production on the QS system. Unlike activation, which can affect other cells, repression acts privately: the de-repression of QS in comQ cells is intracellular and only affects mutant cells lacking ComQ. As a result, the QS signal mutants have an overly responsive QS system and overproduce the secondary metabolite surfactin in the presence of the signal. This surfactin overproduction is associated with a strong fitness cost, as resources are diverted away from primary metabolism. Therefore, by acting as a private QS repressor, ComQ may be protected against evolutionary competition from loss-of-function mutations. Additionally, we find that surfactin participates in a social selection mechanism that targets signal null mutants in coculture with signal producers. Our study shows that by pleiotropically combining intracellular and extracellular signaling, bacteria may generate evolutionarily stable QS systems.