Molecular Genetics of Biofilm Formation

描述（由申请方提供）：表面相关细菌群体通常被称为生物膜。在大多数自然环境中，细菌主要存在于生物膜中，但多年来对细菌生理学的研究主要集中在生物膜状态。广泛认识到，生物膜影响无数的环境，从水管留置装置在医院的病人，导致越来越多的兴趣在调查的分子机制的形成和维护这些社区。从迄今为止描述的生物膜形成策略的多样性中，出现了许多知识，使我们能够为这种现象制定一个一般假设：“生物膜形成是一个发育过程，其中细菌经历了从游牧单细胞状态到定居多细胞状态的调节生活方式转换，随后的生长导致结构化社区和细胞分化。“这里提出的实验代表了我们使用孢子形成细菌枯草芽孢杆菌对这一中心假设进行严格测试的努力。对于运动细菌，从游牧生活方式到定居生活方式的转变通常需要关闭运动性，伴随着细胞外基质的合成。虽然人们普遍认为基质生产和运动是相互排斥的，但对于大多数细菌物种来说，生活方式转换的分子机制仍然是未知的。通过遗传学和生物化学方法的结合，我们已经开始确定的分子调控电路，管理从运动细胞的过渡到矩阵封闭的定居社区的B。枯草杆菌。我们将继续应用遗传学和生物化学方法来解决以下问题：（1）主调节因子控制生活方式转换的分子机制，（2）细胞外基质的组装，以及（3）生物膜内发生的时空组织和细胞分化过程。

DESCRIPTION (provided by applicant): Populations of surface-associated bacteria are commonly referred to as biofilms. In most natural settings bacteria are found predominantly in biofilms, yet for many years studies of bacterial physiology focused primarily on the planktonic state. The widespread recognition that biofilms impact myriad environments, from water pipes to indwelling devices in hospital patients, has led to an increase interest in investigating the molecular mechanisms underlying the formation and maintenance of these communities. From the diversity of biofilm formation strategies thus far described emerges much knowledge that allows us to formulate a general hypothesis for this phenomenon: "Biofilm formation is a developmental process in which bacteria undergo a regulated lifestyle switch from a nomadic unicellular state to a sedentary multicellular state where subsequent growth results in structured communities and cellular differentiation." The experiments proposed here represent our efforts to critically test aspects of this central hypothesis using the sporulating bacterium, Bacillus subtilis. For motile bacteria, the lifestyle switch from a nomadic to a sedentary existence usually entails the shutdown of motility with the concomitant synthesis of the extracellular matrix. While it is generally agreed that matrix production and motility are mutually exclusive, the molecular mechanisms that underlie the lifestyle switch remain virtually unknown for most bacterial species. Through a combination of genetic and biochemical approaches, we have begun to identify the molecular regulatory circuitry that governs the transition from motile cells to matrix-enclosed sedentary communities of B. subtilis. We will continue to apply genetic and biochemical approaches to address questions regarding: (1) The molecular mechanism via which a master regulator controls the lifestyle switch, (2) The assembly of the extracellular matrix, and (3) The spatio-temporal organization and cellular differentiation processes that occur within the biofilm.