Host glycoprotein Gp96 and scavenger receptor SREC interact with PorB of disseminating Neisseria gonorrhoeae in an epithelial invasion pathway
Host glycoprotein Gp96 and scavenger receptor SREC interact with PorB of disseminating Neisseria gonorrhoeae in an epithelial invasion pathway
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DOI：
10.1016/j.chom.2007.11.002
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发表时间：
2007-12-01
影响因子：
30.3
通讯作者：
Rudel, Thomas
中科院分区：
文献类型：
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作者：
Rechner, Cindy;Kuehlewein, Christiane;Rudel, Thomas
淋病奈瑟菌在感染过程中表达许多介导细菌粘附和侵袭的表面蛋白。表达主要外膜孔蛋白PorB（PorB(IA)）血清型A的淋球菌经常从严重传播感染患者中分离出来。PorB（IA）在低磷酸盐条件下触发有效的粘附和侵袭，模拟全身血流感染。在这里，我们确定了人热休克糖蛋白Gp96和清扫剂受体SREC是PorB（IA）特异性受体。表达PorB（IA）的淋球菌，而不是那些表达PorB血清型B的淋球菌，与纯化的天然或重组的Gp96结合。宿主细胞中Gp96的缺失阻止了黏附，但显著引发淋球菌入侵。此外，这种入侵被清除受体的化学抑制剂阻断，我们确定SREC是参与PorB（IA）依赖性入侵的清除受体。因此，我们建立了Gp96作为抗侵袭因子和SRECs作为受体介导高侵袭性传播淋球菌进入宿主细胞。
Neisseria gonorrhoeae expresses numerous surface proteins that mediate bacterial adherence and invasion during infection. Gonococci expressing serotype A of the major outer membrane porin PorB (PorB(IA)) are frequently isolated from patients with severe disseminating infections. PorB(IA) triggers efficient adherence and invasion under low phosphate conditions mimicking systemic bloodstream infections. Here, we identify the human heat shock glycoprotein Gp96 and the scavenger receptor SREC as PorB(IA)-specific receptors. Gonococci expressing PorB(IA), but not those expressing PorB serotype B instead, bind to purified native or recombinant Gp96. Depletion of Gp96 from host cells prevented adherence but significantly triggered gonococcal invasion. Furthermore, such invasion was blocked by chemical inhibitors of scavenger receptors, and we identified SREC as the scavenger receptor involved in PorB(IA)-dependant invasion. Thus, we establish Gp96 as an anti-invasion factor and SRECs as receptors mediating host cell entry of highly invasive disseminating gonococci.