SEQUENCE CHANGES IN THE PILUS SUBUNIT LEAD TO TROPISM VARIATION OF NEISSERIA-GONORRHOEAE TO HUMAN TISSUE
SEQUENCE CHANGES IN THE PILUS SUBUNIT LEAD TO TROPISM VARIATION OF NEISSERIA-GONORRHOEAE TO HUMAN TISSUE
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DOI：
10.1111/j.1365-2958.1994.tb00435.x
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发表时间：
1994-08-01
影响因子：
3.6
通讯作者：
NORMARK, S
中科院分区：
文献类型：
--
作者：
JONSSON, AB;ILVER, D;NORMARK, S
淋病奈瑟菌的菌毛与上皮细胞上的细菌附着增加有关，并经历了阶段和抗原变异。淋球菌菌毛的阶段变化可以通过菌毛蛋白结构基因pilE中的重组事件或通过PilC（存在两个基因座的菌毛生物发生蛋白）表达中的开/关开关来实现。我们研究了N.携带结构上确定的PilE和PilC蛋白的淋病MS 11衍生物和突变体。N.淋病奈瑟菌与福尔马林固定的组织切片的结合模式类似于使用不同来源的活上皮细胞系获得的结合模式。含有不同pilE序列的有菌毛淋球菌克隆在与角膜和结膜组织结合的效率方面彼此差异很大，但与宫颈和子宫内膜组织的结合效果相同。此外，结合数据表明PilC表达本身，即没有pill，不能赋予细菌结合，并且PilC 1或PilC 2的表达不赋予细菌细胞不同的结合特性。在人的子宫颈、子宫内膜、角膜、肠、胃、中脑和脑膜等组织中表达可能的纤毛淋球菌受体，但在人的肾脏中不表达。用蛋白酶K预处理靶组织显著降低淋球菌结合，而用神经氨酸酶和偏高碘酸盐预处理，其切割碳水化合物中邻位羟基之间的碳-碳键，不影响淋球菌的附着。这些数据表明，N.淋病对人组织的作用可能是由具有蛋白质特征的真核受体介导的，并且菌毛亚基序列可能在与人角膜的相互作用中起重要作用。
Pill of Neisseria gonorrhoeae are correlated with increased bacterial attachment to epithelial cells and undergo both phase and antigenic variation. Phase variation of gonococcal pill can be brought about by recombination events in the pilin structural gene, pilE, or by the on/off switch in expression of PilC, a pilus biogenesis protein for which two loci exist. We have studied the binding to epithelial cell lines and to fixed tissue sections of N. gonorrhoeae MS11 derivatives and mutants carrying structurally defined PilE and PilC proteins. In situ binding studies of N. gonorhoeae to formalin-fixed tissue sections resulted in a binding pattern similar to that obtained using viable epithelial cell lines of different origin. Piliated gonococcal clones, containing different pilE sequences, varied dramatically from one another in their efficiencies at binding to corneal and conjunctival tissue, but bound equally well to cervical and endometrial tissues. Further, the binding data suggested that PilC expression by itself, i.e. without pill, cannot confer bacterial binding and that expression of either PilC1 or PilC2 does not confer different binding properties to the bacterial cells. Possible receptors for piliated gonococci were expressed in human tissues, such as cervix, endometrium, cornea, intestine, stomach, mid-brain and meninges, but not in human kidney. Pretreatment of the target tissues with Proteinase K decreased the gonococcal binding dramatically, whereas pretreatment with neuraminidase and meta-periodate, which cleave carbon-carbon linkages between vicinal hydroxyl groups in carbohydrates, did not affect attachment of gonococci. These data argue that pilus-dependent attachment of N. gonorrhoeae to human tissue may be mediated by a eukaryotic receptor having protein characteristics, and that the pilus subunit sequence may play an important role in the interaction with human cornea.