The position of phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae affects binding and sensitivity to C-reactive protein-mediated killing
The position of phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae affects binding and sensitivity to C-reactive protein-mediated killing
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DOI：
10.1046/j.1365-2958.2000.01707.x
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发表时间：
2000-01-01
影响因子：
3.6
通讯作者：
Weiser, JN
中科院分区：
文献类型：
--
作者：
Lysenko, E;Richards, JC;Weiser, JN
流感嗜血杆菌的盖子基因座控制环境胆碱以磷酸胆碱（ChoP）的形式掺入脂多糖（LPS）以及该结构的相变。 Chop 是血清中急性期反应物 C 反应蛋白 (CRP) 的靶标，当与生物体结合时，CRP 会通过激活补体来介导杀伤作用。对流感嗜血菌 LPS 寡糖区域的结构分析表明，Chop 在 Ed 和 Eagan 菌株中的不同链延伸上与不同己糖残基连接。 Chop 分子环境的差异影响单克隆抗体 12D9 定义的表位，并与 LicD（一种推定的二磷酸核苷胆碱转移酶）内的多态性相关。在不同的链延伸上用 Chop 交换两个菌株之间的 licD 基因足以改变其位置。无论遗传背景如何，己糖上的 ChoP 和庚糖 III 上的等位基因变异体对 CRP 介导的血清杀菌活性敏感，而不是庚糖 I。 CRP 介导的杀伤作用的差异与人血清中 CRP 与整个细菌结合的差异相关。这表明，除了涉及相变的机制之外，寡糖内的结构重排也有助于逃避先天性和获得性免疫。
The lid locus of Haemophilus influenzae controls the incorporation of environmental choline into lipopolysaccharide (LPS) as phosphorylcholine (ChoP) as well as the phase variation of this structure. Chop is the target of an acute phase reactant in serum, C-reactive protein (CRP), which mediates killing through the activation of complement when bound to the organism. Structural analysis of the oligosaccharide region of the H. influenzae LPS showed that Chop is linked to different hexose residues on different chain extensions in strains Ed and Eagan. Differences in the molecular environment of Chop affect the epitope defined by monoclonal antibody 12D9 and were associated with polymorphisms within LicD, a putative diphosphonucleoside choline transferase. Exchanging the licD genes between the two strains with Chop on different chain extensions was sufficient to switch its position. Allelic variants with ChoP on a hexose on heptose III rather than heptose I were sensitive to CRP-mediated serum bactericidal activity regardless of the genetic background. Differences in CRP-mediated killing correlated with differences in the binding of CRP from human serum to whole bacteria. This suggests that, in addition to the mechanism involving phase variation, the structural rearrangements within the oligosaccharide contribute to evasion of innate and acquired immunity.