Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection
Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection
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DOI：
10.1038/ncomms5718
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发表时间：
2014-08-01
影响因子：
16.6
通讯作者：
Eulalio, Ana
中科院分区：
文献类型：
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作者：
Maudet, Claire;Mano, Miguel;Eulalio, Ana
越来越多的证据表明miRNAs在细菌病原体和宿主细胞之间的分子相互作用中发挥着重要作用。在这里，我们使用miRNA模拟库进行基于荧光显微镜的筛选，并证明miRNAs调节沙门氏菌感染。MiR-15miRNA家族的几个成员是17个更有效地抑制沙门氏菌感染的miRNAs之一。我们发现，在沙门氏菌感染过程中，这些miRNAs通过抑制转录因子E2F1而下调。对miR-15家族靶点的分析表明，细胞周期蛋白D1的下调以及随后的G1/S转换的促进是沙门氏菌细胞内增殖的关键。此外，沙门氏菌还可诱导感染细胞的G2/M期停滞，进一步促进其复制。总体而言，这些发现揭示了一种机制，即沙门氏菌通过主动调节宿主细胞miRNAs来控制细胞周期进程，从而使宿主细胞更容易受到感染。
Increasing evidence suggests an important role for miRNAs in the molecular interplay between bacterial pathogens and host cells. Here we perform a fluorescence microscopy-based screen using a library of miRNA mimics and demonstrate that miRNAs modulate Salmonella infection. Several members of the miR-15 miRNA family were among the 17 miRNAs that more efficiently inhibit Salmonella infection. We discovered that these miRNAs are downregulated during Salmonella infection, through the inhibition of the transcription factor E2F1. Analysis of miR-15 family targets revealed that derepression of cyclin D1 and the consequent promotion of G1/S transition are crucial for Salmonella intracellular proliferation. In addition, Salmonella induces G2/M cell cycle arrest in infected cells, further promoting its replication. Overall, these findings uncover a mechanism whereby Salmonella renders host cells more susceptible to infection by controlling cell cycle progression through the active modulation of host cell miRNAs.