Role of MUC5B during Group B Streptococcal Vaginal Colonization.

Role of MUC5B during Group B Streptococcal Vaginal Colonization.
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DOI:
10.1128/mbio.00039-22
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发表时间:
2022-04-26
期刊:
影响因子:
6.4
通讯作者:
Doran, Kelly S.
Doran, Kelly S.
中科院分区:
生物学1区
文献类型:
--
作者:
Burcham, Lindsey R.;Bath, Jade R.;Werlang, Caroline A.;Lyon, Laurie M.;Liu, Naoko;Evans, Christopher;Ribbeck, Katharina;Doran, Kelly S.

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女性生殖道(FRT)是一个复杂的环境,富含粘蛋白糖蛋白,在下面的上皮细胞表面形成密集的网络。B族链球菌(GBS)在25-30%的健康妇女中无症状地定殖,但在妊娠期间可引起子宫内上行感染或在出生时传播给新生儿以引起侵袭性疾病。虽然宫颈阴道粘膜是GBS定植的天然部位,但GBS与粘蛋白之间的特异性相互作用仍不清楚。在这里,我们首次证明了MUC 5 B直接与GBS相互作用,并通过抑制细菌附着到人上皮细胞和GBS定植小鼠模型中从阴道到子宫的Ascension来促进屏障功能。对暴露于MUC 5 B的GBS的RNA测序分析鉴定了128个差异表达的GBS基因,包括菌毛岛-2b(PI-2b)位点的上调。我们随后表明,PI-2b是重要的GBS附着到生殖细胞,结合到固定的粘蛋白,阴道定植在体内。我们的研究结果表明,虽然MUC 5 B在宿主防御中起着重要的作用,GBS上调皮利响应粘蛋白,以帮助促进持久性在阴道内,说明病原体和宿主之间的动态相互作用。
The female reproductive tract (FRT) is a complex environment, rich in mucin glycoproteins that form a dense network on the surface of the underlying epithelia. Group B Streptococcus (GBS) asymptomatically colonizes 25–30% of healthy women, but during pregnancy can cause ascending infection in utero or be transmitted to the newborn during birth to cause invasive disease. Though the cervicovaginal mucosa is a natural site for GBS colonization, the specific interactions between GBS and mucins remain unknown. Here we demonstrate for the first time that MUC5B interacts directly with GBS and promotes barrier function by inhibiting both bacterial attachment to human epithelial cells and ascension from the vagina to the uterus in a murine model of GBS colonization. RNA sequencing analysis of GBS exposed to MUC5B identified 128 differentially expressed GBS genes, including upregulation of the pilus island-2b (PI-2b) locus. We subsequently show that PI-2b is important for GBS attachment to reproductive cells, binding to immobilized mucins, and vaginal colonization in vivo. Our results suggest that while MUC5B plays an important role in host defense, GBS upregulates pili in response to mucins to help promote persistence within the vaginal tract, illustrating the dynamic interplay between pathogen and host.
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