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Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

机译:由于卵巢控制下的因素,不透明蛋白增加女性生殖道淋病奈瑟菌的适应性

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The neisserial opacity (Opa) proteins are a family of antigenically distinct outer membrane proteins that undergo phase-variable expression. Opa+ variants of Neisseria gonorrhoeae strain FA1090 are selected in a cyclical pattern from the lower genital tract of estradiol-treated mice. Here we show that cyclical recovery of Opa+ gonococci does not occur in ovariectomized mice; therefore, the reproductive cycle plays a role in the selection kinetics in vivo. As predicted by the selection pattern shown by wild-type gonococci, we demonstrated that a constitutive Opa-expressing strain was more fit than an Opa-deficient mutant in the early and late phases of infection. We found no evidence that Opa-mediated colonization selects for Opa+ variants during murine infection based on adherence assays with cultured murine epithelial cells. We also tested the hypothesis that complement selects for Opa protein expression during infection. Although some Opa+ variants of a serum-sensitive derivative of strain FA1090 were more resistant to the bactericidal activity of normal human serum, selection for Opa expression was not abrogated in C3-depleted mice. Finally, as previously reported, Opa+ gonococci were more sensitive to serine proteases. Thus, proteases or protease inhibitors may contribute to the observed in vivo selection pattern. We concluded that Opa proteins promote persistence of N. gonorrhoeae in the female genital tract and that opa gene phase variation allows gonococci to evade or capitalize upon unidentified host factors of the mammalian reproductive cycle. This work revealed an intimate interaction between pathogen and host and provides evidence that hormonally related factors shape bacterial adaptation.
机译:奈瑟球菌不透明性(Opa)蛋白是一类抗原不同的外膜蛋白,它们经历相变表达。从雌二醇治疗小鼠的下生殖道中以周期性模式选择淋病奈瑟氏球菌菌株FA1090的Opa + 变体。在这里,我们显示在切除卵巢的小鼠中不会发生Opa + 淋球菌的周期性恢复。因此,生殖循环在体内选择动力学中起作用。如野生型淋球菌显示的选择模式所预测的,我们证明在感染的早期和晚期,组成型Opa表达菌株比Opa缺陷型菌株更适合。我们没有证据表明基于培养的鼠上皮细胞的粘附测定,在鼠感染过程中,Opa介导的定殖会选择Opa + 变异。我们还测试了在感染过程中补体选择Opa蛋白表达的假说。尽管菌株FA1090的血清敏感衍生物的某些Opa + 变体对正常人血清的杀菌活性具有更强的抵抗力,但在C3耗竭的小鼠中,Opa表达的选择并未消失。最后,如先前报道,Opa + 淋球菌对丝氨酸蛋白酶更敏感。因此,蛋白酶或蛋白酶抑制剂可能有助于观察到的体内选择模式。我们得出的结论是,Opa蛋白可促进 N的持久性。雌性生殖道中的淋病菌,而 opa 基因的相变使淋球菌可以逃避或利用哺乳动物生殖周期的未知宿主因子。这项工作揭示了病原体与宿主之间的密切相互作用,并提供了激素相关因素影响细菌适应性的证据。

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