Bacterial Division and the Dynamics of the Z-ring

描述（由申请人提供）：对药物治疗产生耐药性的致病微生物是一个日益严重的公共卫生问题。结核病、疟疾和耳部感染只是传统抗生素药物难以治疗的疾病中的几个例子。最近发现的细菌细胞骨架具有形状定义功能，为抗菌治疗提供了新的分子靶点。事实上，累积的结果现在表明，细菌含有类似于肌动蛋白和微管蛋白的蛋白质，尽管没有发现细胞骨架马达蛋白类似物。特别地，原核蛋白FtsZ是分裂环（Z环）的主要组分。环是动态维护的。在分裂周期结束时，环收缩以将细胞分离成子细胞。使用经过实验验证的计算方法，我们解决了Z环动力学中的3个核心问题： 1)Z形环在体内是如何形成的？2)收缩E需要多大的力。大肠杆菌细胞在中间点？3)Z环收缩的机制是什么？在没有分子马达的情况下，它是如何产生力的？为了回答这些问题，我们提出了定量模型，联合收割机相结合的弹性特性的FtsZ长丝与FtsZ的水解化学。该模型需要输入参数，这些参数是从体内活细胞测量获得的。定量理论模型的Z形环组件和动态将直接进行实验测试。Z环收缩是大多数细菌中常见的分裂机制。揭示的收缩机制可能导致开发针对病原菌分裂周期的新型抗生素药物。

DESCRIPTION (provided by applicant): Disease-causing microbes that have become resistant to drug therapy are an increasing public health problem. Tuberculosis, malaria, and ear infections are just a few examples of the diseases that have become difficult to treat with traditional antibiotic drugs. The recent discovery of a bacterial cytoskeleton with shape-defining function provides new molecular targets for anti-bacterial treatments. Indeed, cumulating results now suggest that bacteria contain proteins that are similar to actin and tubulin, although no cytoskeletal motor protein analogs have been found. A primary function of the prokaryotic cytoskeleton is in cell division (cytokinesis). In particular, the prokaryotic protein FtsZ is the major component of the division ring (Z-ring). The ring is dynamically maintained. At the end of the division cycle, the ring contracts to separate the cell into daughter cells. Using a computational approach validated by experiments, we address 3 central questions in Z-ring dynamics: 1) How does the Z-ring form in vivo? 2) How much force is needed to constrict E. coli cells at mid-point? 3) What is the mechanism of Z-ring contraction and how does it generate force without molecular motors? To answer these questions, we propose quantitative models that combine the elastic properties of the FtsZ filaments with the hydrolysis chemistry of FtsZ. The models require input parameters which are obtained from in vivo living-cell measurements. Quantitative theoretical models of the Z-ring assembly and dynamics will be directly tested experimentally. Z-ring contraction is a common division mechanism found in most bacteria. The revealed contraction mechanism could lead to the development of novel antibiotic drugs that target the division cycle of pathogenic bacteria.