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金黄色葡萄球菌细胞壁磷壁酸和荚膜多糖的功能与调控。

Function and regulation of Staphylococcus aureus wall teichoic acids and capsular polysaccharides.

机构信息

Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.

Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.

出版信息

Int J Med Microbiol. 2019 Sep;309(6):151333. doi: 10.1016/j.ijmm.2019.151333. Epub 2019 Jul 18.

Abstract

Staphylococcus aureus produces different secondary cell wall glycopolymers such as wall teichoic acids (WTA) and capsular polysaccharides (CP). These structures play an important role in S. aureus colonization, pathogenesis and bacterial evasion of the host immune defences. To fulfil their diverse functions, biosynthesis of both glycopolymers has to be tightly controlled. Regulation of WTA biosynthesis and modification is only partially understood. The transcription factor MgrA and the two-component systems (TCS) Agr, GraRS, and ArlRS control WTA export, chain-length and modification. CP synthesis is determined by transcriptional and post-transcriptional regulatory circuits. On the transcriptional level expression of the capA-P operon is mainly driven by the alternative Sigma factor B and modulated by several transcriptional factors and TCS. Post-transcriptional mechanisms are in place to avoid conflict between precursor usage by the CP synthesis machinery and the synthesis machinery of other cell wall glycopolymers. The complex interplay of these regulatory systems determines the peculiar, strictly temporal expression of CP in the late growth phase and the high degree of phenotypic heterogeneity. Differential expression of CP, WTA and its modification systems during infection and colonisation are likely important for disease development, immune escape and survival within the host.

摘要

金黄色葡萄球菌产生不同的次级细胞壁糖聚合物,如壁磷壁酸(WTA)和荚膜多糖(CP)。这些结构在金黄色葡萄球菌的定植、发病机制和细菌逃避宿主免疫防御中起着重要作用。为了发挥其多样化的功能,两种糖聚合物的生物合成都必须受到严格的控制。WTA 生物合成和修饰的调控仅部分被理解。转录因子 MgrA 和两个组件系统(TCS)Agr、GraRS 和 ArlRS 控制 WTA 的输出、链长和修饰。CP 的合成由转录和转录后调控回路决定。在转录水平上,capA-P 操纵子的表达主要由替代 Sigma 因子 B 驱动,并受几个转录因子和 TCS 调节。转录后机制的存在是为了避免 CP 合成机制与其他细胞壁糖聚合物合成机制之间的前体使用发生冲突。这些调控系统的复杂相互作用决定了 CP 在生长后期的特殊、严格的时间表达以及表型异质性的高度。在感染和定植过程中,CP、WTA 及其修饰系统的差异表达可能对疾病发展、免疫逃避和宿主内生存至关重要。

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