Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 38; pp. 15479 - 15484
• Main Authors: Deng, Yinyue, Schmid, Nadine, Wang, Chao, Wang, Jianhe, Pessi, Gabriella, Wu, Donghui, Lee, Jasmine, Aguilar, Claudio, Ahrens, Christian H., Chang, Changqing, Song, Haiwei, Eberl, Leo, Zhang, Lian-Hui
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.09.2012; National Acad Sciences
• Subjects: bacterial motility; Bacterial physiology; Bacterial proteins; Bacterial Proteins - metabolism; biofilm; Biofilms; Biological Sciences; Burkholderia cenocepacia; Burkholderia cenocepacia - genetics; Burkholderia cenocepacia - metabolism; Cell Communication; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Dimerization; Fatty acids; Fatty Acids, Monounsaturated - chemistry; Gene expression; Genotype & phenotype; guanosine monophosphate; Guanosine Monophosphate - chemistry; Microorganisms; Models, Genetic; Molecules; Mutagenesis; mutants; Mutation; pathogens; Perception; Phenotype; Phenotypes; Physiology; Protein Binding; Quorum sensing; Quorum Sensing - genetics; Receptors; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Sensors; Signal Transduction; Virulence; Xanthomonas campestris
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1205037109

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.