Bacterial cell wall architecture and dynamics

细菌能够呈现出无数不同的形状，这一特性由它们的细胞壁决定。细胞壁就像一个外部骨架，不仅是形状确定所必需的，而且是保持细胞存活所必需的，因为它能够承受相当大的内力，否则细胞就会破裂。对于大多数细菌来说，细胞壁的主要结构元素是一种名为肽聚糖(PG)的聚合物。PG对细菌来说是独一无二的，对保持细菌的生命至关重要。青霉素和万古霉素等细胞壁抗生素令人难以置信地广泛使用，阻止了PG的产生，说明了PG的重要性。PG是一个包裹在细胞周围的大的袋状分子，虽然非常强大，但也是动态的，允许细胞生长和分裂。尽管PG在化学上只是由相对简单的构建块组成，但如何组装这些构建块来产生能够实现PG的许多功能的体系结构，在很大程度上仍然难以捉摸。我们使用了一种高分辨率显微镜技术，它提供了关于PG结构的令人兴奋的新的和意想不到的信息。最初，在杆状枯草芽孢杆菌中，我们发现了环绕细胞圆柱体的材料绳索，提供了力量。此外，在细胞分裂的地方，一块复杂的材料板以明显的螺旋状铺设。我们对圆形细菌金黄色葡萄球菌的进一步研究显示了一种非常不同的螺纹和小球状结构。正是这些特点，使得细胞能够解决在保持细胞完整性的同时允许生长的工程问题。拟议的项目将采取跨越生物、化学和物理学科的综合方法，以确定从分子到细胞水平的PG的架构。我们将解决微生物学中的基本问题，这些问题是细菌生长和繁殖能力的核心。

Bacteria are able to assume a myriad of different shapes, a property governed by their cell wall. The cell wall is like an external skeleton not only required for shape determination but also for keeping the cell alive as it is able to withstand the considerable internal forces which would otherwise rupture the cell. The major structural element of the cell wall for most bacteria is a polymer called peptidoglycan (PG). PG is unique to the bacteria and is essential for keeping the bacteria alive. This importance of PG is illustrated by the incredibly wide use of cell wall antibiotics such as penicillin and vancomycin, which prevent PG production. PG is a single large, bag-like molecule that surrounds the cell and whilst very strong is also dynamic to allow the cells to grow and divide. Even though PG is chemically only made of relatively simple building blocks how these are assembled to produce an architecture able to fulfil the many functions of PG has remained largely elusive. We have used a high-resolution microscopy technique that has provided exciting new and unexpected information as to the architecture of the PG. Initially in the rod shaped bacterium Bacillus subtilis we have found cables of material running round the cylinder of the cell providing strength. Also where the cell divides, a complex plate of material is laid down in an apparent spiral. Our further work in the round bacterium Staphylococcus aureus has shown a very different architecture of whorls and small knobbles. It is these features, which allow the cells to solve their engineering problems of maintaining cell integrity whilst allowing growth. The proposed project will take an integrated approach across the biological, chemical and physical disciplines to determine the architecture of PG from the molecular to the cellular level. We will address fundamental questions in microbiology that lie at the heart of the ability of bacteria to grow and proliferate.