Reduction of the Peptidoglycan Crosslinking Causes a Decrease in Stiffness of the Staphylococcus aureus Cell Envelope
Reduction of the Peptidoglycan Crosslinking Causes a Decrease in Stiffness of the Staphylococcus aureus Cell Envelope
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DOI：
10.1016/j.bpj.2014.07.029
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发表时间：
2014-09-02
影响因子：
3.4
通讯作者：
Jacobs, Karin
中科院分区：
文献类型：
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作者：
Loskill, Peter;Pereira, Pedro M.;Jacobs, Karin
我们已经使用原子力显微镜（AFM）探测肽聚糖交联减少对金黄色葡萄球菌细胞壁弹性的影响，这是特别感兴趣的抗菌化疗的目标。青霉素结合蛋白4（PBP 4）是一种非必需的转肽酶，是S.金黄色。重要的是，这种蛋白质是社区获得性耐甲氧西林沙门氏菌β-内酰胺类耐药所必需的。金黄色葡萄球菌（MRSA）菌株，但不是在医院获得性MRSA菌株。使用AFM以一种新的模式记录力/距离曲线，我们观察到PBP 4的缺失以及伴随的肽聚糖交联的减少导致S.金黄色细胞壁。重要的是，在不存在PBP 4的情况下，在社区获得性和医院获得性MRSA菌株中均观察到细胞壁刚度的降低，表明高水平的肽聚糖交联调节S.两种类型的临床相关菌株中的金黄色葡萄球菌细胞包膜。此外，我们能够证明所应用的方法能够分离细胞壁性质和膨压。
We have used atomic-force microscopy (AFM) to probe the effect of peptidoglycan crosslinking reduction on the elasticity of the Staphylococcus aureus cell wall, which is of particular interest as a target for antimicrobial chemotherapy. Penicillin-binding protein 4 (PBP4) is a nonessential transpeptidase, required for the high levels of peptidoglycan crosslinking characteristic of S. aureus. Importantly, this protein is essential for beta-lactam resistance in community-acquired, methicillin-resistant S. aureus (MRSA) strains but not in hospital-acquired MRSA strains. Using AFM in a new mode for recording force/distance curves, we observed that the absence of PBP4, and the concomitant reduction of the peptidoglycan crosslinking, resulted in a reduction in stiffness of the S. aureus cell wall. Importantly, the reduction in cell wall stiffness in the absence of PBP4 was observed both in community-acquired and hospital-acquired MRSA strains, indicating that high levels of peptidoglycan crosslinking modulate the overall structure and mechanical properties of the S. aureus cell envelope in both types of clinically relevant strains. Additionally, we were able to show that the applied method enables the separation of cell wall properties and turgor pressure.