Differential RNA-seq of Vibrio cholerae identifies the VqmR small RNA as a regulator of biofilm formation

Differential RNA-seq of Vibrio cholerae identifies the VqmR small RNA as a regulator of biofilm formation
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DOI:
10.1073/pnas.1500203112
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发表时间:
2015-02-17
影响因子:
11.1
通讯作者:
Bassler, Bonnie L.
Bassler, Bonnie L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Papenfort, Kai;Foerstner, Konrad U.;Bassler, Bonnie L.

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群体感应(QS)是一种细胞间的交流过程,使细菌能够在个人和集体生活方式之间转换。QS控制霍乱弧菌的毒力和生物膜的形成,霍乱弧菌是霍乱的病原体。对野生型霍乱弧菌和一株锁定的低细胞密度qs突变株的差异RNA测序(RNA-seq)确定了7240个转录起始点,其中47%是在反义方向启动的。共有107个转录本似乎不编码蛋白质,这表明它们指定了调控RNA。我们关注了一个这样的文本,我们将其命名为VqmR。VqmR位于编码DNA结合转录因子的vqmA基因的上游。突变和微阵列分析表明,VqmA激活vqmR转录,vqmR编码一个调控RNA,VqmR直接控制至少8个mRNA靶点,包括rtx(毒素重复序列)毒素基因和vpsT转录调节生物膜产生。我们发现VqmR通过抑制vpsT抑制生物膜的形成。总之,这些数据为我们提供了霍乱弧菌转录起始位点的第一个全球注释,并强调了转录后调控对这种人类病原体集体行为的重要性。
Quorum sensing (QS) is a process of cell-to-cell communication that enables bacteria to transition between individual and collective lifestyles. QS controls virulence and biofilm formation in Vibrio cholerae, the causative agent of cholera disease. Differential RNA sequencing (RNA-seq) of wild-type V. cholerae and a locked low-cell-density QS-mutant strain identified 7,240 transcriptional start sites with similar to 47% initiated in the antisense direction. A total of 107 of the transcripts do not appear to encode proteins, suggesting they specify regulatory RNAs. We focused on one such transcript that we name VqmR. vqmR is located upstream of the vqmA gene encoding a DNA-binding transcription factor. Mutagenesis and microarray analyses demonstrate that VqmA activates vqmR transcription, that vqmR encodes a regulatory RNA, and VqmR directly controls at least eight mRNA targets including the rtx (repeats in toxin) toxin genes and the vpsT transcriptional regulator of biofilm production. We show that VqmR inhibits biofilm formation through repression of vpsT. Together, these data provide to our knowledege the first global annotation of the transcriptional start sites in V. cholerae and highlight the importance of posttranscriptional regulation for collective behaviors in this human pathogen.