A simple mechanism for integration of quorum sensing and cAMP signalling in Vibrio cholerae.
A simple mechanism for integration of quorum sensing and cAMP signalling in Vibrio cholerae.
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DOI：
10.7554/elife.86699
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发表时间：
2023-07-06
期刊：
影响因子：
7.7
通讯作者：
Grainger DC
中科院分区：
文献类型：
--
作者：
Walker LM;Haycocks JRJ;Van Kessel JC;Dalia TN;Dalia AB;Grainger DC
许多细菌利用群体感应来控制生活方式的变化。这个过程是由微生物衍生的“自动诱导”信号分子调节的，这些分子在局部环境中积累。单个细胞通过感知自诱导剂的丰度来推断种群密度，并相应地改变它们的行为。在霍乱弧菌中，群体感应信号通过磷酸化转导到转录因子LuxO。未磷酸化的LuxO允许HapR的表达，这改变了全球基因表达模式。在这项工作中，我们绘制了霍乱弧菌LuxO和HapR的全基因组分布图谱。LuxO有一个小的规则子，而HapR靶向32个位点。许多HapR靶点与调节碳饥饿转录反应的cAMP受体蛋白（CRP）的位点一致。这种重叠，在其他弧菌物种中也很明显，是由每个因子结合的DNA序列的相似性造成的。在共享位点，HapR和CRP同时接触双螺旋，并且通过两个因子的直接相互作用稳定结合。重要的是，这涉及到CRP表面，该表面通常与RNA聚合酶接触以刺激转录。因此，HapR可以阻断CRP的转录激活。因此，通过在共享位点上相互作用，HapR和CRP整合了群体感应和cAMP信号的信息来控制基因表达。这可能允许霍乱弧菌在水生环境和人类宿主之间的过渡期间调节基因亚群。
Many bacteria use quorum sensing to control changes in lifestyle. The process is regulated by microbially derived ‘autoinducer’ signalling molecules, that accumulate in the local environment. Individual cells sense autoinducer abundance, to infer population density, and alter their behaviour accordingly. In Vibrio cholerae, quorum-sensing signals are transduced by phosphorelay to the transcription factor LuxO. Unphosphorylated LuxO permits expression of HapR, which alters global gene expression patterns. In this work, we have mapped the genome-wide distribution of LuxO and HapR in V. cholerae. Whilst LuxO has a small regulon, HapR targets 32 loci. Many HapR targets coincide with sites for the cAMP receptor protein (CRP) that regulates the transcriptional response to carbon starvation. This overlap, also evident in other Vibrio species, results from similarities in the DNA sequence bound by each factor. At shared sites, HapR and CRP simultaneously contact the double helix and binding is stabilised by direct interaction of the two factors. Importantly, this involves a CRP surface that usually contacts RNA polymerase to stimulate transcription. As a result, HapR can block transcription activation by CRP. Thus, by interacting at shared sites, HapR and CRP integrate information from quorum sensing and cAMP signalling to control gene expression. This likely allows V. cholerae to regulate subsets of genes during the transition between aquatic environments and the human host.