Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification.
Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification.
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DOI：
10.1038/s41467-018-05494-w
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发表时间：
2018-08-23
影响因子：
16.6
通讯作者：
Henriques-Normark B
中科院分区：
文献类型：
--
作者：
Pathak A;Bergstrand J;Sender V;Spelmink L;Aschtgen MS;Muschiol S;Widengren J;Henriques-Normark B
肺炎链球菌通过表达免疫保护性的多糖胶囊和因子H(FH)结合蛋白来逃避C3介导的调理和效应功能。在这里，我们使用超分辨显微镜、突变体和功能分析来展示这两种防御机制是如何在细菌细胞表面上功能和空间上协调的。我们发现肺炎球菌被膜在细胞壁隔膜中含量较少，提供C3/C3b进入潜在的亲核靶标。为了避免C3b在分裂隔处的沉积和包膜下的横向放大，需要将FH结合蛋白PSPC定位在分裂部位。大多数肺炎球菌株只有一种PSPC蛋白，但在定植和疾病中成功的谱系可能有两种，我们发现它们对毒力的影响是不同的。我们发现，这些FH募集蛋白相对于分裂间隔和被膜层的空间定位有助于肺炎球菌抵抗补体介导的吞噬作用，形成攻击膜的复合体，并发挥粘附素的功能。肺炎链球菌通过表达免疫保护性多糖胶囊和因子H结合蛋白来逃避补体系统的作用。在这里，帕萨克等人。表明这两种防御机制在细菌细胞表面的功能和空间上是协调的。
Streptococcus pneumoniae evades C3-mediated opsonization and effector functions by expressing an immuno-protective polysaccharide capsule and Factor H (FH)-binding proteins. Here we use super-resolution microscopy, mutants and functional analysis to show how these two defense mechanisms are functionally and spatially coordinated on the bacterial cell surface. We show that the pneumococcal capsule is less abundant at the cell wall septum, providing C3/C3b entry to underlying nucleophilic targets. Evasion of C3b deposition at division septa and lateral amplification underneath the capsule requires localization of the FH-binding protein PspC at division sites. Most pneumococcal strains have one PspC protein, but successful lineages in colonization and disease may have two, PspC1 and PspC2, that we show affect virulence differently. We find that spatial localization of these FH-recruiting proteins relative to division septa and capsular layer is instrumental for pneumococci to resist complement-mediated opsonophagocytosis, formation of membrane-attack complexes, and for the function as adhesins. Streptococcus pneumoniae evades the action of the complement system by expressing an immuno-protective polysaccharide capsule as well as Factor H-binding proteins. Here, Pathak et al. show that these two defence mechanisms are functionally and spatially coordinated on the bacterial cell surface.
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DOI：
10.1073/pnas.1319066110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Kandaswamy, Kumaravel;Liew, Tze Horng;Kline, Kimberly A.
通讯作者：
Kline, Kimberly A.
影响因子：
2.9
作者：
Karlsson, R;Katsamba, PS;Myszka, DG
通讯作者：
Myszka, DG
影响因子：
3.4
作者：
Comeau, Jonathan W. D.;Costantino, Santiago;Wiseman, Paul W.
通讯作者：
Wiseman, Paul W.
影响因子：
30.3
作者：
Dalia AB;Weiser JN
通讯作者：
Weiser JN
影响因子：
6.4
作者：
GORDON, DL;JOHNSON, GM;HOSTETTER, MK
通讯作者：
HOSTETTER, MK