PMID- 29158389 OWN - NLM STAT- MEDLINE DCOM- 20180627 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 114 IP - 49 DP - 2017 Dec 5 TI - Burkholderia cenocepacia integrates cis-2-dodecenoic acid and cyclic dimeric guanosine monophosphate signals to control virulence. PG - 13006-13011 LID - 10.1073/pnas.1709048114 [doi] AB - 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 Burkholderia cenocepacia, the QS signal receptor RpfR degrades intracellular c-di-GMP when it senses the QS signal cis-2-dodecenoic acid, also called Burkholderia diffusible signal factor (BDSF), as a proxy for high cell density. However, it was unclear how this resulted in control of BDSF-regulated phenotypes. Here, we found that RpfR forms a complex with a regulator named GtrR (BCAL1536) to enhance its binding to target gene promoters under circumstances where the BDSF signal binds to RpfR to stimulate its c-di-GMP phosphodiesterase activity. In the absence of BDSF, c-di-GMP binds to the RpfR-GtrR complex and inhibits its ability to control gene expression. Mutations in rpfR and gtrR had overlapping effects on both the B. cenocepacia transcriptome and BDSF-regulated phenotypes, including motility, biofilm formation, and virulence. These results show that RpfR is a QS signal receptor that also functions as a c-di-GMP sensor. This protein thus allows B. cenocepacia to integrate information about its physical and chemical surroundings as well as its population density to control diverse biological functions including virulence. This type of QS system appears to be widely distributed in beta and gamma proteobacteria. FAU - Yang, Chunxi AU - Yang C AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China. AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China. AD - Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou 510642, China. AD - School of Biological Sciences, Nanyang Technological University, Singapore 637551. FAU - Cui, Chaoyu AU - Cui C AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China. AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China. AD - Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou 510642, China. FAU - Ye, Qiumian AU - Ye Q AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China. AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China. FAU - Kan, Jinhong AU - Kan J AD - Center for Crop Germplasm Resources, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China. FAU - Fu, Shuna AU - Fu S AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China. AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China. FAU - Song, Shihao AU - Song S AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China. AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China. FAU - Huang, Yutong AU - Huang Y AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China. AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China. FAU - He, Fei AU - He F AD - Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou 510642, China. FAU - Zhang, Lian-Hui AU - Zhang LH AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China. AD - Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou 510642, China. FAU - Jia, Yantao AU - Jia Y AD - State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. FAU - Gao, Yong-Gui AU - Gao YG AD - School of Biological Sciences, Nanyang Technological University, Singapore 637551. FAU - Harwood, Caroline S AU - Harwood CS AUID- ORCID: 0000-0003-4450-5177 AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China; csh5@u.washington.edu ydeng@scau.edu.cn. AD - Department of Microbiology, University of Washington, Seattle, WA 98195. FAU - Deng, Yinyue AU - Deng Y AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, China; csh5@u.washington.edu ydeng@scau.edu.cn. AD - Guangdong Innovative Research Team of Sociomicrobiology, College of Agriculture, South China Agricultural University, Guangzhou 510642, China. AD - Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou 510642, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171120 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (2-dodecenoic acid) RN - 0 (Bacterial Proteins) RN - 0 (Fatty Acids, Monounsaturated) RN - 61093-23-0 (bis(3',5')-cyclic diguanylic acid) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Animals MH - Bacterial Load MH - Bacterial Proteins/*genetics/metabolism MH - Biofilms/growth & development MH - Burkholderia Infections/microbiology/pathology MH - Burkholderia cenocepacia/*genetics/growth & development/*pathogenicity MH - Cyclic GMP/*analogs & derivatives/metabolism MH - Fatty Acids, Monounsaturated/*metabolism MH - *Gene Expression Regulation, Bacterial MH - Mice MH - Mutation MH - Phenotype MH - Quorum Sensing/*genetics MH - Signal Transduction MH - Virulence PMC - PMC5724260 OTO - NOTNLM OT - BDSF signal OT - bacterial virulence OT - c-di-GMP OT - quorum sensing COIS- The authors declare no conflict of interest. EDAT- 2017/11/22 06:00 MHDA- 2018/06/28 06:00 PMCR- 2018/06/05 CRDT- 2017/11/22 06:00 PHST- 2017/11/22 06:00 [pubmed] PHST- 2018/06/28 06:00 [medline] PHST- 2017/11/22 06:00 [entrez] PHST- 2018/06/05 00:00 [pmc-release] AID - 1709048114 [pii] AID - 201709048 [pii] AID - 10.1073/pnas.1709048114 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):13006-13011. doi: 10.1073/pnas.1709048114. Epub 2017 Nov 20.