title: Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover.
abstract: 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.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore. ydeng@imcb.a-star.edu.sg
authors.forename: Yinyue
authors.initials: Y
authors.lastname: Deng
authors.forename: Nadine
authors.initials: N
authors.lastname: Schmid
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Jianhe
authors.initials: J
authors.lastname: Wang
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pessi
authors.forename: Donghui
authors.initials: D
authors.lastname: Wu
authors.forename: Jasmine
authors.initials: J
authors.lastname: Lee
authors.forename: Claudio
authors.initials: C
authors.lastname: Aguilar
authors.forename: Christian H
authors.initials: CH
authors.lastname: Ahrens
authors.forename: Changqing
authors.initials: C
authors.lastname: Chang
authors.forename: Haiwei
authors.initials: H
authors.lastname: Song
authors.forename: Leo
authors.initials: L
authors.lastname: Eberl
authors.forename: Lian-Hui
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D057508:Burkholderia cenocepacia / Q000235:genetics* / Q000378:metabolism; D002450:Cell Communication; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D019281:Dimerization; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D006157:Guanosine Monophosphate / Q000737:chemistry*; D008957:Models, Genetic; D016296:Mutagenesis; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D053038:Quorum Sensing / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D014774:Virulence
chemical_list: C527562:2-dodecenoic acid; D001426:Bacterial Proteins; D005229:Fatty Acids, Monounsaturated; D011956:Receptors, Cell Surface; C062025:bis(3',5')-cyclic diguanylic acid; D006157:Guanosine Monophosphate; D006152:Cyclic GMP