MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT.

MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT.
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MAPS 将肌动蛋白靶向效应子 SteC 的调节整合到沙门氏菌小 RNA PinT 的毒力控制网络中

DOI:
10.1016/j.celrep.2021.108722
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发表时间:
2021
期刊:
影响因子:
8.8
通讯作者:
Vogel J
Vogel J
中科院分区:
生物学1区
文献类型:
--
作者:
Correia Santos S;Bischler T;Westermann AJ;Vogel J

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要全面了解小RNA(sRNA)对细菌毒力的贡献,需要了解它们在感染相关条件下的靶向套件。在这里,我们采取综合的方法来捕获Hfq相关的sRNA PinT,一个已知的转录后定时器的两个主要的毒力程序ofSalmonella enterica.Using MS2亲和纯化和RNA测序(MAPS)的目标,我们确定PinT配体在细菌在体外条件下模仿感染周期的特定阶段,并在细菌内生长的巨噬细胞。这揭示了PinT介导的分泌效应激酶SteC的翻译抑制,这在以前的靶点搜索中没有被注意到。使用遗传,生物化学和显微镜检测,我们提供的证据PinT介导的抑制steCmRNA,最终延迟肌动蛋白重排在感染的宿主细胞。我们的研究结果支持PinT作为沙门氏菌毒力的核心转录后调节因子的作用,并说明了需要补充方法来揭示sRNA的完整靶标套件。
A full understanding of the contribution of small RNAs (sRNAs) to bacterial virulence demands knowledge of their target suites under infection-relevant conditions. Here, we take an integrative approach to capturing targets of the Hfq-associated sRNA PinT, a known post-transcriptional timer of the two major virulence programs ofSalmonella enterica.Using MS2 affinity purification and RNA sequencing (MAPS), we identify PinT ligands in bacteria underin vitroconditions mimicking specific stages of the infection cycle and in bacteria growing inside macrophages. This reveals PinT-mediated translational inhibition of the secreted effector kinase SteC, which had gone unnoticed in previous target searches. Using genetic, biochemical, and microscopic assays, we provide evidence for PinT-mediated repression ofsteCmRNA, eventually delaying actin rearrangements in infected host cells. Our findings support the role of PinT as a central post-transcriptional regulator inSalmonellavirulence and illustrate the need for complementary methods to reveal the full target suites of sRNAs.
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