Yinyue Denga,1,2, Nadine Schmidb,1, Chao Wanga, Jianhe Wanga, Gabriella Pessib, Donghui Wua, Jasmine Leea, Claudio Aguilarb, Christian H. Ahrensc, Changqing Changa, Haiwei Songa, Leo Eberlb,2, and Lian-Hui Zhanga,2.
a- Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore
b- Department of Microbiology, University of Zürich, CH-8008 Zürich, Switzerland
c- Institute of Molecular Life Sciences, University of Zürich, CH-8057 Zürich, Switzerland
1- Y.D. and N.S. have contributed equally to this work.
2- Corresponding authors
Published ahead of print in PNAS on 4th September 2012.
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 swarmingmotility, 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.
Figure Legend: ITC analysis of the molecular interaction between BDSF and RpfR. (A) ITC titration of 20 μM RpfR with 200 μM BDSF in PBS buffer at 21 °C. (B) ITC titration of 20 μM RpfR with 200 μM of the saturated isomer of BDSF in PBS buffer at 21 °C.
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