Regulation of Autolysins

细菌很小，通常约为1/1000毫米大小，但非常强大，能够在不同的环境中生存和繁殖。有些细菌会导致严重的感染，需要用抗生素治疗，但许多细菌对人类健康有益，或者在维持地球上健康的生态系统方面发挥着重要作用。细菌的定义特征之一是它们的细胞被膜，其中包含由肽聚糖组成的细胞壁。肽聚糖在细胞膜周围形成一层，以保护细胞免受几个大气压的内部压力造成的破裂。肽聚糖的第二个主要作用是维持细菌细胞的特定形状（球形、棒状或其他形状）。为了实现这些功能，肽聚糖层以网状结构完全包裹细胞膜，承受由内部压力引起的大部分应力。我们的一些最好的抗生素，例如青霉素，抑制肽聚糖的合成，这间接导致层缺陷，随后细胞解体（裂解）。为了生长和分裂，细菌需要扩大其承受压力的肽聚糖层，这不仅需要合成新的肽聚糖并将其附着到现有的层上。还需要肽聚糖水解酶打开网中的网孔，以允许新肽聚糖插入并扩展其表面。这些水解酶也被称为自溶素，因为它们能够在某些条件下引起自身细胞的裂解。已知革兰氏阴性模式细菌大肠杆菌有20多种自溶素，分为三大类，但它们的潜在危险活动在细胞中是如何控制的，对其中一些知之甚少。该提案旨在从分子上了解模型细菌中关键自溶素的调节以及它们如何在抗生素存在下解除调节。

Bacteria are small, often around 1/1000 of a millimetre in size, and yet remarkably robust to be able to survive and propagate in different environments. Some bacteria can cause severe infections that need to be treated with antibiotics but many bacteria are beneficial to human health or play a major role in maintaining healthy ecosystems on the earth. One of the defining features of bacteria is their cell envelope which contains the cell wall made of peptidoglycan. Peptidoglycan forms a layer around the cell membrane to protect the cell from bursting due to its internal pressure of several atmospheres. A second major role of peptidoglycan is to maintain the specific shape (sphere, rod or other) of a bacterial cell. To fulfil these functions the peptidoglycan layer completely encases the cell membrane with a net-like structure, bearing much of the stress caused by the internal pressure. Some of our best antibiotics, for example Penicillin, inhibit the synthesis of peptidoglycan which indirectly causes defects in the layer followed by the disintegration (lysis) of the cell.In order to grow and divide, bacteria need to enlarge their stress-bearing peptidoglycan layer, which does not only require the the synthesis of new peptidoglycan and its attachment to the existing layer. Peptidoglycan hydrolases are also needed to open meshes in the net to allow the insertion of the new peptidoglycan and expand its surface. These hydrolases are also called autolysins because they are capable of causing the lysis of the own cell under certain conditions. The Gram-negative model bacterium Escherichia coli is known to have more than 20 autolysins, categorized in three major classes, but how their potentially dangerous activities are controlled in the cell is only poorly understood for some of them. This proposal aims to gain a molecular understanding of the regulation of key autolysins in the model bacterium and how they become deregulated in the presence of an antibiotic.