YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
YebC regulates variable surface antigen VlsE expression and is required for host immune evasion in Borrelia burgdorferi.
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YebC 调节可变表面抗原 VlsE 表达，是伯氏疏螺旋体宿主免疫逃避所必需的
DOI：
10.1371/journal.ppat.1008953
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发表时间：
2020-10
期刊：
影响因子：
6.7
通讯作者：
Lou Y
中科院分区：
文献类型：
--
作者：
Zhang Y;Chen T;Raghunandanan S;Xiang X;Yang J;Liu Q;Edmondson DG;Norris SJ;Yang XF;Lou Y
伯氏疏螺旋体（Borrelia burgdorferi）是莱姆病病原体，通过逃避宿主免疫反应而引起持续感染。经历抗原变异的表面暴露脂蛋白 VlsE 的差异表达是伯氏疏螺旋体采用的关键免疫逃避策略。大多数研究集中在 VlsE 抗原变异的机制上，但对 VlsE 调控和调节差异性 vlsE 表达的因子知之甚少。在本研究中，我们研究了 BB0025，一种假定的 YebC 家族转录调节因子（因此在本文中将 BB0025 命名为伯氏疏螺旋体的 YebC）。我们在伯氏疏螺旋体感染菌株中构建了 yebC 突变体和补充菌株。 yebC 突变体可以感染免疫功能低下的 SCID 小鼠，但不能感染免疫功能正常的小鼠，这表明 YebC 在逃避宿主适应性免疫方面发挥着重要作用。 RNA-seq 分析确定 vlsE 是表达受 YebC 影响最大的基因之一。定量 RT-PCR 和蛋白质印迹分析证实 vlsE 表达依赖于 YebC。在体外，YebC 和 VlsE 共同调节以响应生长温度。在小鼠中，yebC 和 vlsE 均与 ospC 反向表达，以响应宿主适应性免疫反应。此外，EMSA 证明 YebC 直接结合 vlsE 启动子，表明存在直接转录控制。这些数据表明，YebC 是一种新的调节因子，可调节 vlsE 和其他对哺乳动物宿主中螺旋体感染和免疫逃避很重要的基因的表达。
Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the mechanism of VlsE antigen variation, but little is known about VlsE regulation and factor(s) that regulates differential vlsE expression. In this study, we investigated BB0025, a putative YebC family transcriptional regulator (and hence designated BB0025 as YebC of B. burgdorferi herein). We constructed yebC mutant and complemented strain in an infectious strain of B. burgdorferi. The yebC mutant could infect immunocompromised SCID mice but not immunocompetent mice, suggesting that YebC plays an important role in evading host adaptive immunity. RNA-seq analyses identified vlsE as one of the genes whose expression was most affected by YebC. Quantitative RT-PCR and Western blot analyses confirmed that vlsE expression was dependent on YebC. In vitro, YebC and VlsE were co-regulated in response to growth temperature. In mice, both yebC and vlsE were inversely expressed with ospC in response to the host adaptive immune response. Furthermore, EMSA proved that YebC directly binds to the vlsE promoter, suggesting a direct transcriptional control. These data demonstrate that YebC is a new regulator that modulates expression of vlsE and other genes important for spirochetal infection and immune evasion in the mammalian host.
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影响因子：
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作者：
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发表时间：
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影响因子：
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