Schmid Nadine, Suppiger Angela, Steiner Elisabeth, Pessi Gabriella, Kaever Volkhard, Fazli Mustafa, Tolker-Nielsen Tim, Jenal Urs, Eberl Leo
Institute of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland.
Research Core Unit Metabolomics, Hannover Medical School, Hannover, Germany.
Microbiology (Reading). 2017 May;163(5):754-764. doi: 10.1099/mic.0.000452. Epub 2017 May 3.
The opportunistic human pathogen Burkholderia cenocepacia H111 uses two chemically distinct signal molecules for controlling gene expression in a cell density-dependent manner: N-acyl-homoserine lactones (AHLs) and cis-2-dodecenoic acid (BDSF). Binding of BDSF to its cognate receptor RpfR lowers the intracellular c-di-GMP level, which in turn leads to differential expression of target genes. In this study we analysed the transcriptional profile of B. cenocepacia H111 upon artificially altering the cellular c-di-GMP level. One hundred and eleven genes were shown to be differentially expressed, 96 of which were downregulated at a high c-di-GMP concentration. Our analysis revealed that the BDSF, AHL and c-di-GMP regulons overlap for the regulation of 24 genes and that a high c-di-GMP level suppresses expression of AHL-regulated genes. Phenotypic analyses confirmed changes in the expression of virulence factors, the production of AHL signal molecules and the biosynthesis of different biofilm matrix components upon altered c-di-GMP levels. We also demonstrate that the intracellular c-di-GMP level determines the virulence of B. cenocepacia to Caenorhabditis elegans and Galleria mellonella.
机会性人类病原体洋葱伯克霍尔德菌H111利用两种化学性质不同的信号分子以细胞密度依赖性方式控制基因表达：N-酰基高丝氨酸内酯（AHLs）和顺式-2-十二碳烯酸（BDSF）。BDSF与其同源受体RpfR结合会降低细胞内c-di-GMP水平，进而导致靶基因的差异表达。在本研究中，我们分析了人为改变细胞内c-di-GMP水平后洋葱伯克霍尔德菌H111的转录谱。结果显示111个基因存在差异表达，其中96个基因在高c-di-GMP浓度下表达下调。我们的分析表明，BDSF、AHL和c-di-GMP调控子在调控24个基因方面存在重叠，并且高c-di-GMP水平会抑制AHL调控基因的表达。表型分析证实了c-di-GMP水平改变后毒力因子表达、AHL信号分子产生以及不同生物膜基质成分生物合成的变化。我们还证明细胞内c-di-GMP水平决定了洋葱伯克霍尔德菌对秀丽隐杆线虫和大蜡螟的毒力。
