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在与大脑内皮细胞相互作用时,B组菌转录基因组.

Nadine Vollmuth1, Bailey E Bridgers1, Madelyn L Armstrong1

  • 1Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA.

Journal of bacteriology
|May 21, 2024
PubMed
概括

乙组链球菌 (GBS) 脑膜炎是新生儿脑膜炎的主要原因. RNA-seq分析确定了GBS毒性因子,其中一个关键的调节器codY被降低,导致细菌粘附度增加和入侵大脑内皮细胞.

关键词:
B组的链球菌.链球菌的 agalactiaeae 是一个细菌.血脑屏障 血脑屏障 血脑屏障 血脑屏障大脑内皮细胞是脑内皮细胞.转录组 (transcriptome) 是一个转录组.

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科学领域:

  • 微生物学 微生物学
  • 神经科学是一个神经科学.
  • 遗传学 遗传学是一种遗传学.

背景情况:

  • 乙组链球菌 (GBS) 是新生儿细菌性脑膜炎的主要原因.
  • GBS通过穿越血脑屏障 (BBB) 和脑膜-脑脊液屏障 (mBCSFB) 侵入中枢神经系统.
  • 以前的GBS病毒性因子鉴定依赖于遗传查.

研究的目的:

  • 在与大脑内皮细胞 (BEC) 相互作用时使用RNA测序 (RNA-seq) 识别与GBS病毒性相关的基因.
  • 为了研究下调基因,特别是 codY 在 GBS 病变发生过程中的作用.
  • 为未来的GBS-BBB相互作用研究提供转录组数据和验证结果.

主要方法:

  • 与诱导多能干细胞衍生的BECs (iBECs) 共同培养的GBS的RNA测序 (RNA-seq).
  • 定量PCR (qPCR) 用于验证codY表达的RNA-seq发现.
  • 在两个体外BEC模型中生成和表型分析GBS codY突变.

主要成果:

  • 在2068个GBS基因中,430个在BEC相互作用时表现出差异性表达,其中大多数 (360) 是下调的.
  • 在GBS-BEC相互作用期间,转录抑制剂codY被显著下调.
  • 在BEC模型中,缺乏codY的GBS突变体表现出增加的粘附和入侵能力.

结论:

  • 在BEC相互作用期间,RNA-seq是识别GBS毒性调节器的宝贵工具.
  • 降低codY的调节是GBS发病的一个关键事件,增强细菌BBB穿越.
  • 这项研究提供了一个经过验证的转录组数据集,为GBS-BBB相互作用途径提供了洞察力.