Sepulchre Jacques-A, Reverchon Sylvie, Nasser William
Institut Non Linéaire de Nice, UNSA-CNRS, 1361 Route des Lucioles, 06560 Valbonne Sophia Antipolis, France.
J Theor Biol. 2007 Jan 21;244(2):239-57. doi: 10.1016/j.jtbi.2006.08.010. Epub 2006 Aug 22.
Building up from experimental knowledge of the regulatory network of the pel genes in the bacteria E. chrysanthemi, we propose for the first time a qualitative modeling of the infectious transition of this bacteria when it is hosted in a plant. We show that this infectious transition can be understood as the excitable dynamics of a metabolico-genetic network. Our mathematical model can account for the main phases which are observed in the onset of the pathogenecity by Erwinia chrysanthemi, namely the silent, latent and virulent stages. Like in many infectious agents, the silent state corresponds to the growth phase of the bacteria, where they multiply without significantly producing molecules which could trigger a counter attack of the invaded host. The latent stage is characterized by a moderate but unequivocal expression of the virulence gene, waiting for a number of conditions which have to fulfill in order to trigger a fully developed infection. In the virulent state the bacteria synthesize a massive production of virulence factors including pectate lyases (Pel) which favor the invasion of the host plant tissues. Our model is able to show cases of transitions from the silent to the virulent stages of the infection, using the method of the piecewise-affine (PA) differential equations and its implementation in the genetic network analyser software (GNA). The obtained qualitative dynamics of the models are consistent with the current experimental data about this system. Moreover it can be interpreted with respect to the relatively complex structure of the binding sites of pel. From the biological point of view, our simulations validate the picture that the promoter of pel has evolved to form a security device preventing a hastened expression of these virulent genes. This first modeling of the regulation of pel genes opens the way to new confrontations between theoretical ideas with experiments and possible strategies to fight the soft-rot disease of plants.
基于对菊欧文氏菌中pel基因调控网络的实验知识，我们首次提出了该细菌在植物宿主体内感染转变的定性模型。我们表明，这种感染转变可理解为代谢 - 遗传网络的可激发动力学。我们的数学模型能够解释菊欧文氏菌致病性起始阶段观察到的主要阶段，即沉默、潜伏和致病阶段。与许多感染因子一样，沉默状态对应于细菌的生长阶段，在此阶段它们大量繁殖，但不会大量产生可引发被入侵宿主反击的分子。潜伏阶段的特征是毒力基因有适度但明确的表达，等待一系列条件满足以引发全面感染。在致病状态下，细菌大量合成包括果胶酸裂解酶（Pel）在内的毒力因子，这些因子有利于入侵宿主植物组织。我们的模型能够通过分段仿射（PA）微分方程方法及其在遗传网络分析仪软件（GNA）中的实现，展示感染从沉默阶段到致病阶段的转变情况。模型得到的定性动力学与关于该系统的当前实验数据一致。此外，它可以根据pel结合位点相对复杂的结构进行解释。从生物学角度来看，我们的模拟验证了pel启动子已进化形成一种安全装置以防止这些毒力基因过早表达的观点。pel基因调控的首次建模为理论观点与实验之间的新对抗以及对抗植物软腐病的可能策略开辟了道路。
