Laboratoire d'Informatique, Signaux et Systèmes Complexes de Sophia-Antipolis (I3S), Université de Nice-Sophia Antipolis and Centre National de la Recherche Scientifique, Sophia-Antipolis, France.
PLoS One. 2012;7(1):e24651. doi: 10.1371/journal.pone.0024651. Epub 2012 Jan 31.
Cyclolipopeptides (CLPs) are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene (plcC) and not restored by plcC complementation. Their production is also subject to phenotypic variation. We used a modelling approach with Boolean networks, which takes into account all these observations concerning CLP production without any assumption on the topology of the considered network. Intensive computation yielded numerous models that satisfy these properties. All models minimizing the number of components point to a bistability in CLP production, which requires the presence of a yet unknown key self-inducible regulator. Furthermore, all suggest that a set of yet unexplained phenotypic variants might also be due to this epigenetic switch. The simplest of these Boolean networks was used to propose a biological regulatory network for CLP production. This modelling approach has allowed a possible regulation to be unravelled and an unusual behaviour of CLP production in P. fluorescens to be explained.
环脂肽(CLPs)是许多荧光假单胞菌菌株产生的生物表面活性剂。CLP 的产生至少受到 GacA/GacS 双组分途径的调控,但完整的调控网络仍知之甚少。在临床菌株 MFN1032 中,CLP 的产生被磷脂酶 C 基因(plcC)的突变所消除,并且 plcC 互补不能恢复其产生。它们的产生也受到表型变异的影响。我们使用布尔网络建模方法,该方法考虑了与 CLP 产生有关的所有这些观察结果,而无需对所考虑网络的拓扑结构做出任何假设。大量的计算产生了许多满足这些特性的模型。所有最小化组件数量的模型都指向 CLP 产生的双稳定性,这需要存在一个未知的关键自诱导调节剂。此外,所有模型都表明,一组尚未解释的表型变体也可能归因于这种表观遗传开关。这些布尔网络中最简单的一个被用来提出 CLP 产生的生物调控网络。这种建模方法揭示了一种可能的调控机制,并解释了荧光假单胞菌中 CLP 产生的异常行为。