Regulation of Autolysins

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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.