CHLAMYDIA-TRACHOMATIS HOST-CELL INTERACTIONS - ROLE OF THE CHLAMYDIAL MAJOR OUTER-MEMBRANE PROTEIN AS AN ADHESIN
CHLAMYDIA-TRACHOMATIS HOST-CELL INTERACTIONS - ROLE OF THE CHLAMYDIAL MAJOR OUTER-MEMBRANE PROTEIN AS AN ADHESIN
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DOI：
10.1128/iai.58.4.1017-1025.1990
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发表时间：
1990-04-01
影响因子：
3.1
通讯作者：
CALDWELL, HD
中科院分区：
文献类型：
--
作者：
SU, H;WATKINS, NG;CALDWELL, HD
沙眼衣原体的主要外膜蛋白 (MOMP) 具有四个对称间隔的可变结构域 (VD I 至 IV)，其序列因血清型而异。这些 VD 的表面暴露部分包含连续序列，这些序列既是血清分型决定簇，又是中和抗体的体内靶位点。先前使用沙眼衣原体 B 表面蛋白水解的研究表明，该血清型 MOMP 的 VD II 和 IV 与衣原体与宿主细胞的附着有关。在本研究中，我们使用针对 B 血清型 MOMP 的 VD II 和 IV 抗原决定簇的特异性单克隆抗体 (MAb) 来进一步研究 MOMP 在衣原体附着于宿主细胞中的作用。分别位于暴露的 VD II 和 IV 中的血清型和亚种特异性表位特异的单克隆抗体，通过阻断衣原体附着，中和了仓鼠肾细胞的衣原体感染性。我们对这些单克隆抗体进行了放射性碘标记，并用它们来确定衣原体基体上表面暴露的 VD II 和 IV 表位的数量和拓扑结构。 VD II 和 IV 各自包含大约 2.86 倍。 104 个带负电的位点位于衣原体细胞表面附近。这些研究表明单克隆抗体通过抑制与宿主细胞的静电相互作用来阻断衣原体附着。我们研究了热失活对衣原体附着和 MOMP 构象的影响。热灭活的衣原体无法附着到宿主细胞上，并且位于沙眼衣原体血清型 MOMP 的 VD IV 内的不可接近的不变疏水九肽序列中表现出共信息变化。这些发现表明，除了静电相互作用之外，MOMP 的常见疏水成分也有助于衣原体与宿主细胞的结合。因此，我们提出 MOMP 通过促进与宿主细胞的非特异性（静电和疏水）相互作用而发挥衣原体粘附素的作用。表面可接近的带负电荷的VD似乎在静电结合中很重要，而VD IV的不变区域可能提供表面下的疏水抑制，从而通过疏水相互作用进一步促进衣原体与宿主细胞的结合。
The major outer membrane protein (MOMP) of Chlamydia trachomatis is characterized by four symmetrically spaced variable domains (VDs I to IV) whose sequences vary among serotypes. The surface-exposed portions of these VDs contain contiguous sequences that are both serotyping determinants and in vivo target sites for neutralizing antibodies. Previous studies using surface proteolysis of C. trachomatis B implicated VDs II and IV of the MOMP of this serotype in the attachment of chlamydiae to host cells. In this study, we used monoclonal antibodies (MAbs) specific to antigenic determinants located in VDs II and IV of the MOMP of serotype B to further investigate the role of the MOMP in the attachment of chlamydiae to host cells. MAbs specific to serotype- and subspecies-specific epitopes located in exposed VDs II and IV, respectively, neutralized chlamydial infectively for hamster kidney cells by blocking chlamydial attachment. We radioiodinated these MAbs and used them to determine the number and topology of the surface-exposed VDs II and IV epitopes on chlamydial elementary bodies. VDs II and IV each comprised approximately 2.86 .times. 104 negatively charged sites and were in proximity on the chlamydial cell surface. These studies suggest that the MAbs blocked chlamydial attachment by inhibiting electrostatic interactions with host cells. We examined the effects of thermal inactivation on both chlamydial attachment and conformation of the MOMP. Heat-inactivated chlamydiae failed to attach to host cells and exhibited a coinformational change in an inaccessible invariant hydrophobic nonapeptide sequence located within VD IV of the MOMPs of C. trachomatis serotypes. These findings suggest that in addition to electrostatic interactions, a common hydrophobic component of the MOMP also contributes to the binding of chlamydiae to host cells. Thus, we propose that the MOMP functions as a chlamydial adhesin by promoting nonspecific (electrostatic and hydrophobic) interactions with host cells. Surface-accessible negatively charged VDs appear to be important in electrostatic binding, while the invariant region of VD IV may provide a subsurface hydrophobic depression which further promotes binding of chlamydiae to host cells through hydrophobic interactions.