In vivo selection for Neisseria gonorrhoeae opacity protein expression in the absence of human carcinoembryonic antigen cell adhesion molecules.
In vivo selection for Neisseria gonorrhoeae opacity protein expression in the absence of human carcinoembryonic antigen cell adhesion molecules.
复制标题
在缺乏人癌胚抗原细胞粘附分子的情况下，体内选择淋病奈瑟菌不透明蛋白的表达。
DOI：
10.1128/iai.74.5.2965-2974.2006
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发表时间：
2006
影响因子：
3.1
通讯作者：
Jerse,AnnE
中科院分区：
文献类型：
--
作者：
Simms,AmyN;Jerse,AnnE
奈瑟球菌混浊（Opa）蛋白是介导粘附和侵入人类细胞的相可变的、抗原性不同的外膜蛋白。我们以前报道过淋病奈瑟菌Opa蛋白的表达似乎是在实验性小鼠生殖道感染过程中被选择或诱导的。在这里，我们进一步定义了Opa变体从雌性小鼠下生殖道中回收的动力学，并研究了这一初步观察的基础。我们发现不同Opa表型从小鼠的恢复似乎是周期性的。定义了感染的三个阶段。阴道内接种主要为Opa −淋球菌后，回收的大多数分离株为Opa+（早期）。随后在大多数小鼠中出现Opa+分离株百分比的下降（中期），随后在感染超过8天的小鼠中重新出现Opa+变体（晚期）。我们发现，早期阶段是由于通过构建氯霉素抗性（Cmr）菌株和随后的CmrOpa+群体与野生型（Cms）菌株的更高百分比的Opa −变体混合，选择接种物中预先存在的Opa+变体。相互实验（Opa + Cms细菌加标的Opa − Cmrgonococci）与Opa+变体的选择一致。基于人癌胚抗原细胞粘附分子（Opa蛋白粘附受体的主要类别）在小鼠中的缺失，我们得出结论，在感染早期观察到的对Opa+变体的选择不太可能是由于特异性粘附优势，可能是由于Opa介导的先天防御逃避。
The neisserial opacity (Opa) proteins are phase-variable, antigenically distinct outer membrane proteins that mediate adherence to and invasion of human cells. We previously reported thatNeisseria gonorrhoeaeOpa protein expression appeared to be selected for or induced during experimental murine genital tract infection. Here we further defined the kinetics of recovery of Opa variants from the lower genital tracts of female mice and investigated the basis for this initial observation. We found that the recovery of different Opa phenotypes from mice appears cyclical. Three phases of infection were defined. Following intravaginal inoculation with primarily Opa−gonococci, the majority of isolates recovered were Opa+(early phase). A subsequent decline in the percentage of Opa+isolates occurred in a majority of mice (middle phase) and was followed by a reemergence of Opa+variants in mice that were infected for longer than 8 days (late phase). We showed the early phase was due to selection for preexisting Opa+variants in the inoculum by constructing a chloramphenicol-resistant (Cmr) strain and following CmrOpa+populations mixed with a higher percentage of Opa−variants of the wild-type (Cms) strain. Reciprocal experiments (Opa−Cmrgonococci spiked with Opa+Cmsbacteria) were consistent with selection of Opa+variants. Based on the absence in mice of human carcinoembryonic antigen cell adhesion molecules, the major class of Opa protein adherence receptors, we conclude the observed selection for Opa+variants early in infection is not likely due to a specific adherence advantage and may be due to Opa-mediated evasion of innate defenses.