Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases.
Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases.
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DOI：
10.1128/mbio.00660-15
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发表时间：
2015-07-28
期刊：
影响因子：
6.4
通讯作者：
Foster SJ
中科院分区：
文献类型：
--
作者：
Wheeler R;Turner RD;Bailey RG;Salamaga B;Mesnage S;Mohamad SA;Hayhurst EJ;Horsburgh M;Hobbs JK;Foster SJ
大多数细菌细胞被包裹在细胞壁聚合物肽聚糖的单个大分子中，肽聚糖是形状确定和维持活力所必需的，而肽聚糖生物合成是重要的抗生素靶点。据推测，细胞增大需要通过肽聚糖的协调插入和水解来局部扩张细胞壁。在这里，鉴定了一组（表观氨基葡萄糖苷酶）肽聚糖水解酶，它们是金黄色葡萄球菌细胞增大和正确细胞形态所必需的，证明了这种酶活性的总体重要性。它们是 Atl、SagA、ScaH 和 SagB。这里的主要进展是根据肽聚糖的机械和生化特性解释了观察到的形态缺陷。结果表明，缺乏这些水解酶组的细胞表面硬度增加，并且在缺乏 SagB 的情况下，聚糖链长度显着增加。这表明，除了其既定的作用（例如在细胞分离中）之外，一些水解酶通过使肽聚糖更容易拉伸来实现细胞增大，这提供了第一个直接证据证明细胞增大是通过调节肽聚糖的机械特性而发生的。了解细菌的生长和分裂是一个基本问题，该领域的知识是许多传染病治疗的基础。几乎所有细菌都被肽聚糖大分子包围，肽聚糖包围细胞并保持形状，细菌细胞必须增加该分子的大小才能扩大自身。这不仅需要插入新的肽聚糖单体（这是包括青霉素在内的抗生素的目标过程），还需要破坏现有的键，这是对细胞具有潜在危险的活动。利用金黄色葡萄球菌，我们鉴定出了一组对于细胞增大至关重要的酶。我们证明这些酶是正常生长所必需的，并定义了完成细胞增大的机制，即通过破坏肽聚糖中的键，这降低了细胞壁的硬度，使其能够拉伸和扩张，这一过程可能是许多细菌的基础。
Most bacterial cells are enclosed in a single macromolecule of the cell wall polymer, peptidoglycan, which is required for shape determination and maintenance of viability, while peptidoglycan biosynthesis is an important antibiotic target. It is hypothesized that cellular enlargement requires regional expansion of the cell wall through coordinated insertion and hydrolysis of peptidoglycan. Here, a group of (apparent glucosaminidase) peptidoglycan hydrolases are identified that are together required for cell enlargement and correct cellular morphology of Staphylococcus aureus, demonstrating the overall importance of this enzyme activity. These are Atl, SagA, ScaH, and SagB. The major advance here is the explanation of the observed morphological defects in terms of the mechanical and biochemical properties of peptidoglycan. It was shown that cells lacking groups of these hydrolases have increased surface stiffness and, in the absence of SagB, substantially increased glycan chain length. This indicates that, beyond their established roles (for example in cell separation), some hydrolases enable cellular enlargement by making peptidoglycan easier to stretch, providing the first direct evidence demonstrating that cellular enlargement occurs via modulation of the mechanical properties of peptidoglycan. Understanding bacterial growth and division is a fundamental problem, and knowledge in this area underlies the treatment of many infectious diseases. Almost all bacteria are surrounded by a macromolecule of peptidoglycan that encloses the cell and maintains shape, and bacterial cells must increase the size of this molecule in order to enlarge themselves. This requires not only the insertion of new peptidoglycan monomers, a process targeted by antibiotics, including penicillin, but also breakage of existing bonds, a potentially hazardous activity for the cell. Using Staphylococcus aureus, we have identified a set of enzymes that are critical for cellular enlargement. We show that these enzymes are required for normal growth and define the mechanism through which cellular enlargement is accomplished, i.e., by breaking bonds in the peptidoglycan, which reduces the stiffness of the cell wall, enabling it to stretch and expand, a process that is likely to be fundamental to many bacteria.