Function of Small basic protein (Sbp) in Staphylococcus epidermidis biofilm matrix assembly: molecular mechanisms and spatio-temporal patterning.

多层细菌生物膜结构的组装是一个主要的例子，其中细菌单细胞特性被整合并转化为群体行为，这反过来为单个细胞在不断变化的、潜在的恶劣环境中获胜提供了线索。生物膜形成的一个标志是细胞外基质的产生，事实上，生物膜基质的产生及其功能后果是细菌多细胞涌现功能的突出例子。生物膜基质由过多的各种生物分子组成，称为“基质组”。最近，我们从表皮葡萄球菌生物膜基质制剂中鉴定出了18 kDa的小碱性蛋白（Sbp）。Sbp在生物膜-基质界面和细胞间隙中积累，从而在功能上支持生物膜的形成。此外，sbp敲除突变体表现出惊人的固定生长期缺陷和对糖肽的易感性增加，这两种表型与转录组分析中确定的严格应答基因表达模式一致。现有的证据支持这样的假设，即Sbp基质组装发生在时间和空间上的协调事件中，提供了一个从根本上影响细菌生理的环境。我们将使用高分辨率成像结合生化方法和单细胞技术来剖析Sbp生物膜基质组装的原理，识别和表征相关的相互作用网络，并提供Sbp生物膜基质对葡萄球菌生理学的重要性的见解。在总体背景下，该项目将提供对驱动细菌多细胞性的动力学一般原理的分子见解，以及它们在群体和单细胞水平上与细菌生理学的相互关系。

The assembly of multi-layered bacterial biofilm architectures is a prime example in which bacterial single cell traits are integrated and translated into population behaviour, which in turn provides cues for individual cells to prevail in changing, potentially harsh environments. A hallmark of biofilm formation is production of an extracellular matrix, and in fact, biofilm matrix production and its functional consequences are outstanding examples for emergent functions of bacterial multicellularity. The biofilm matrix consists of a plethora of various biomolecules, referred to as the “matrixome”. Recently, we have identified 18 kDa Small basic protein (Sbp) from S. epidermidis biofilm matrix preparations. Sbp accumulates at the biofilm - substratum interface and in the intercellular space, and thereby functionally supports biofilm formation. In addition, a sbp knock-mutant exhibits striking stationary growth phase defects and increased susceptibility against glycopeptides, both phenotypes being consistent with stringent response gene expression patterns as identified in transciptome analysis. The available evidence supports the hypothesis that Sbp matrix assembly occurs along temporally and spatially orchestrated events, providing an environment which fundamentally affects bacterial physiology. We will use high resolution imaging in combination with biochemical approaches and single cell techniques to dissect principles of Sbp biofilm matrix assembly, identify and characterize involved interaction networks, and to provide insights into the importance of Sbp biofilm matrices for staphylococcal physiology. In the overarching context, the project will provide molecular insights into general principles of dynamics driving bacterial multicellularity, and their inter-relation with bacterial physiology on population and single cell levels.