PMID- 30687272 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 9 DP - 2018 TI - Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia. PG - 3286 LID - 10.3389/fmicb.2018.03286 [doi] LID - 3286 AB - Burkholderia cenocepacia H111 is an opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients. Biofilm formation, motility and virulence of B. cenocepacia are regulated by the second messenger cyclic di-guanosine monophosphate (c-di-GMP). In the present study, we analyzed the role of all 25 putative c-di-GMP metabolizing proteins of B. cenocepacia H111 with respect to motility, colony morphology, pellicle formation, biofilm formation, and virulence. We found that RpfR is a key regulator of c-di-GMP signaling in B. cenocepacia, affecting a broad spectrum of phenotypes under various environmental conditions. In addition, we identified Bcal2449 as a regulator of B. cenocepacia virulence in Galleria mellonella larvae. While Bcal2449 consists of protein domains that may catalyze both c-di-GMP synthesis and degradation, only the latter was essential for larvae killing, suggesting that a decreased c-di-GMP level mediated by the Bcal2449 protein is required for virulence of B. cenocepacia. Finally, our work suggests that some individual proteins play a role in regulating exclusively motility (CdpA), biofilm formation (Bcam1160) or both (Bcam2836). FAU - Richter, Anja M AU - Richter AM AD - Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Fazli, Mustafa AU - Fazli M AD - Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Schmid, Nadine AU - Schmid N AD - Department of Microbiology, University of Zurich, Zurich, Switzerland. FAU - Shilling, Rebecca AU - Shilling R AD - Department of Microbiology, University of Zurich, Zurich, Switzerland. FAU - Suppiger, Angela AU - Suppiger A AD - Department of Microbiology, University of Zurich, Zurich, Switzerland. FAU - Givskov, Michael AU - Givskov M AD - Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore. FAU - Eberl, Leo AU - Eberl L AD - Department of Microbiology, University of Zurich, Zurich, Switzerland. FAU - Tolker-Nielsen, Tim AU - Tolker-Nielsen T AD - Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article DEP - 20190110 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC6335245 OTO - NOTNLM OT - Bcal2449 OT - Burkholderia cenocepacia OT - Cyclic-di-GMP OT - GGDEF EAL domain proteins OT - RpfR OT - biofilm formation OT - motility EDAT- 2019/01/29 06:00 MHDA- 2019/01/29 06:01 PMCR- 2019/01/10 CRDT- 2019/01/29 06:00 PHST- 2018/09/14 00:00 [received] PHST- 2018/12/17 00:00 [accepted] PHST- 2019/01/29 06:00 [entrez] PHST- 2019/01/29 06:00 [pubmed] PHST- 2019/01/29 06:01 [medline] PHST- 2019/01/10 00:00 [pmc-release] AID - 10.3389/fmicb.2018.03286 [doi] PST - epublish SO - Front Microbiol. 2019 Jan 10;9:3286. doi: 10.3389/fmicb.2018.03286. eCollection 2018.