bis(3--5-)-cyclic-diguanylic-acid and 2-dodecenoic-acid

Quorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities.

Topics: Acyl-Butyrolactones; Bacterial Proteins; Biofilms; Burkholderia cenocepacia; Burkholderia Infections; Cyclic GMP; Fatty Acids, Monounsaturated; Gene Expression Regulation, Bacterial; Microbial Sensitivity Tests; Phenotype; Quorum Sensing; Signal Transduction; Virulence

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.

Topics: Acyl-Butyrolactones; Animals; Burkholderia cenocepacia; Caenorhabditis elegans; Cyclic GMP; Fatty Acids, Monounsaturated; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Moths; Quorum Sensing; Signal Transduction; Virulence; Virulence Factors

Quorum sensing (QS) signals are used by bacteria to regulate biological functions in response to cell population densities. Cyclic diguanosine monophosphate (c-di-GMP) regulates cell functions in response to diverse environmental chemical and physical signals that bacteria perceive. In

Topics: Animals; Bacterial Load; Bacterial Proteins; Biofilms; Burkholderia cenocepacia; Burkholderia Infections; Cyclic GMP; Fatty Acids, Monounsaturated; Gene Expression Regulation, Bacterial; Mice; Mutation; Phenotype; Quorum Sensing; Signal Transduction; Virulence

Many bacterial pathogens produce diffusible signal factor (DSF)-type quorum sensing (QS) signals in modulation of virulence and biofilm formation. Previous work on Xanthomonas campestris showed that the RpfC/RpfG two-component system is involved in sensing and responding to DSF signals, but little is known in other microorganisms. Here we show that in Burkholderia cenocepacia the DSF-family signal cis-2-dodecenoic acid (BDSF) negatively controls the intracellular cyclic dimeric guanosine monophosphate (c-di-GMP) level through a receptor protein RpfR, which contains Per/Arnt/Sim (PAS)-GGDEF-EAL domains. RpfR regulates the same phenotypes as BDSF including swarming motility, biofilm formation, and virulence. In addition, the BDSF(-) mutant phenotypes could be rescued by in trans expression of RpfR, or its EAL domain that functions as a c-di-GMP phosphodiesterase. BDSF is shown to bind to the PAS domain of RpfR with high affinity and stimulates its phosphodiesterase activity through induction of allosteric conformational changes. Our work presents a unique and widely conserved DSF-family signal receptor that directly links the signal perception to c-di-GMP turnover in regulation of bacterial physiology.

Topics: Bacterial Proteins; Burkholderia cenocepacia; Cell Communication; Cyclic GMP; Dimerization; Fatty Acids, Monounsaturated; Guanosine Monophosphate; Models, Genetic; Mutagenesis; Mutation; Phenotype; Protein Binding; Quorum Sensing; Receptors, Cell Surface; Signal Transduction; Virulence