School of Biosciences, University of Birmingham, Edgbaston, United Kingdom.
Department of Biology, Indiana University, Bloomington, United States.
Elife. 2023 Jul 6;12:RP86699. doi: 10.7554/eLife.86699.
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 , 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 . 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 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 to regulate subsets of genes during the transition between aquatic environments and the human host.
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“自动诱导剂”信号分子调节的，这些信号分子在局部环境中积累。单个细胞感知自动诱导剂的丰度，以推断种群密度，并相应地改变它们的行为。在，群体感应信号通过磷酸接力传递到转录因子 LuxO。非磷酸化的 LuxO 允许 HapR 的表达，从而改变全局基因表达模式。在这项工作中，我们已经绘制了 LuxO 和 HapR 在的全基因组分布。虽然 LuxO 有一个小的调控基因，但 HapR 的靶标是 32 个基因座。许多 HapR 的靶标与 cAMP 受体蛋白 (CRP) 的结合位点重合，CRP 调节对碳饥饿的转录反应。这种重叠在其他物种中也很明显，这是由于每个因子结合的 DNA 序列相似。在共享的位点上，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 表面通常与 RNA 聚合酶接触以刺激转录。因此，HapR 可以通过 CRP 阻断转录激活。因此，通过在共享位点相互作用，HapR 和 CRP 整合了来自群体感应和 cAMP 信号的信息，以控制基因表达。这可能允许在从水生环境到人体宿主的转变过程中调节基因的子集。
