RT Journal Article SR Electronic(1) A1 Schmid, Nadine A1 Suppiger, Angela A1 Steiner, Elisabeth A1 Pessi, Gabriella A1 Kaever, Volkhard A1 Fazli, Mustafa A1 Tolker-Nielsen, Tim A1 Jenal, Urs A1 Eberl, LeoYR 2017 T1 High intracellular c-di-GMP levels antagonize quorum sensing and virulence gene expression in Burkholderia cenocepacia H111 JF Microbiology, VO 163 IS 5 SP 754 OP 764 DO https://doi.org/10.1099/mic.0.000452 PB Microbiology Society, SN 1465-2080, AB 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., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000452