Coordination of capsule assembly and cell wall biosynthesis in Staphylococcus aureus
Coordination of capsule assembly and cell wall biosynthesis in Staphylococcus aureus
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DOI：
10.1038/s41467-019-09356-x
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发表时间：
2019-03-29
影响因子：
16.6
通讯作者：
Schneider, Tanja
中科院分区：
文献类型：
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作者：
Rausch, Marvin;Deisinger, Julia P.;Schneider, Tanja
革兰氏阳性细胞壁由用阴离子糖共聚物（例如壁磷壁酸和荚膜多糖（CP））官能化的肽聚糖组成。不同的细胞壁聚合物如何以协调的方式组装尚未完全了解。在这里，我们重建金黄色葡萄球菌CP的生物合成，并阐明其与细胞壁生物合成机制的相互作用。我们发现，CapAB酪氨酸激酶复合物通过可逆磷酸化来控制多个酶检查点，以调节也用于肽聚糖生物合成的必需前体的消耗。此外，CapA 1激活蛋白与脂质连接的CP前体相互作用并切割，释放必需的脂质载体十一异戊二烯基磷酸。我们进一步提供了生物化学证据表明，CP的后续附着是通过LytR-CpsA-Psr蛋白家族的成员LcpC，使用肽聚糖前体天然脂质II作为受体底物实现的。Ser/Thr激酶PknB可以感知细胞脂质II水平，负控制CP合成。我们的工作揭示了CP生物合成的多组分革兰氏阳性细胞壁的整合。
The Gram-positive cell wall consists of peptidoglycan functionalized with anionic glycopolymers, such as wall teichoic acid and capsular polysaccharide (CP). How the different cell wall polymers are assembled in a coordinated fashion is not fully understood. Here, we reconstitute Staphylococcus aureus CP biosynthesis and elucidate its interplay with the cell wall biosynthetic machinery. We show that the CapAB tyrosine kinase complex controls multiple enzymatic checkpoints through reversible phosphorylation to modulate the consumption of essential precursors that are also used in peptidoglycan biosynthesis. In addition, the CapA1 activator protein interacts with and cleaves lipid-linked CP precursors, releasing the essential lipid carrier undecaprenyl-phosphate. We further provide biochemical evidence that the subsequent attachment of CP is achieved by LcpC, a member of the LytR-CpsA-Psr protein family, using the peptidoglycan precursor native lipid II as acceptor substrate. The Ser/Thr kinase PknB, which can sense cellular lipid II levels, negatively controls CP synthesis. Our work sheds light on the integration of CP biosynthesis into the multi-component Gram-positive cell wall.