The microRNA Cargo of Human Vaginal Extracellular Vesicles Differentiates Parasitic and Pathobiont Infections from Colonization by Homeostatic Bacteria.

The microRNA Cargo of Human Vaginal Extracellular Vesicles Differentiates Parasitic and Pathobiont Infections from Colonization by Homeostatic Bacteria.
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DOI:
10.3390/microorganisms11030551
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发表时间:
2023-02-21
期刊:
影响因子:
4.5
通讯作者:
Fichorova RN
Fichorova RN
中科院分区:
生物学3区
文献类型:
--
作者:
Cezar-de-Mello PFT;Ryan S;Fichorova RN

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被定义为细菌性阴道病(BV)的阴道微生物组紊乱和阴道毛滴虫(TV)的寄生虫感染(最常见的非病毒性传播病原体)对生殖结果以及感染和癌症的易感性具有明确的不良影响。这些关联的分子机制和抗生素治疗未能减轻不良后果尚未完全阐明。在体外人阴道定植模型中,我们测试了对TV和/或BV细菌的反应将破坏细胞外囊泡(EV)的微(mi)RNA货物的假设,其具有改变与生殖功能、癌症和感染相关的途径的潜力。通过HTG EdgeSeq定量miRNA。利用R.通过miRWalk、STRING、Cytoscape和CytoHubba鉴定验证的基因靶标、途径、蛋白质-蛋白质相互作用网络和枢纽基因。与L.卷曲病毒、TV和BV病原体的大量EV-miRNA失调,超过50%由两种病原体共享。相应的靶向通路、蛋白质相互作用簇和顶部枢纽基因与癌症、感染性疾病、昼夜节律、类固醇激素信号传导、妊娠和生殖组织术语相关。这些数据支持了一个新的概念,即细菌和寄生真核生物干扰人类阴道微生物组可能通过EV-miRNA失调影响生殖健康。
The disturbed vaginal microbiome defined as bacterial vaginosis (BV) and the parasitic infection by Trichomonas vaginalis (TV), the most common non-viral sexually transmitted pathogen, have well-established adverse effects on reproductive outcomes and susceptibility to infection and cancer. Molecular mechanisms underlying these associations and the failure of antibiotic therapy to mitigate adverse consequences are not fully elucidated. In an in vitro human vaginal colonization model, we tested the hypothesis that responses to TV and/or BV-bacteria will disrupt the micro(mi)RNA cargo of extracellular vesicles (EV) with the potential to modify pathways associated with reproductive function, cancer, and infection. miRNAs were quantified by HTG EdgeSeq. MiRNA differential expression (DE) was established in response to TV, the BV signature pathobiont Prevotella bivia and a homeostatic Lactobacillus crispatus with adjusted p < 0.05 using R. Validated gene targets, pathways, protein-protein interaction networks, and hub genes were identified by miRWalk, STRING, Cytoscape, and CytoHubba. In contrast to L. crispatus, TV and the BV pathobiont dysregulated a massive number of EV-miRNAs, over 50% shared by both pathogens. Corresponding target pathways, protein interaction clusters and top hub genes were related to cancer, infectious disease, circadian rhythm, steroid hormone signaling, pregnancy, and reproductive tissue terms. These data support the emerging concept that bacteria and parasitic eukaryotes disturbing the human vaginal microbiome may impact reproductive health through EV-miRNA dysregulation.
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