PMID- 29541628 OWN - NLM STAT- MEDLINE DCOM- 20190325 LR - 20190325 IS - 2235-2988 (Electronic) IS - 2235-2988 (Linking) VI - 8 DP - 2018 TI - A c-di-GMP-Modulating Protein Regulates Swimming Motility of Burkholderia cenocepacia in Response to Arginine and Glutamate. PG - 56 LID - 10.3389/fcimb.2018.00056 [doi] LID - 56 AB - Burkholderia cenocepacia is an opportunistic bacterium that can thrive in different environments, including the amino acid-rich mucus of the cystic fibrosis (CF) lung. B. cenocepacia responds to the nutritional conditions that mimic the CF sputum by increasing flagellin expression and swimming motility. Individual amino acids also induce swimming but not flagellin expression. Here, we show that modulation of the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) levels by the PAS-containing c-di-GMP phosphodiesterase, BCAL1069 (CdpA), regulates the swimming motility of B. cenocepacia K56-2 in response to CF sputum nutritional conditions. Heterologous expression of WspR, a diguanylate cyclase, in B. cenocepacia K56-2 caused an increase in c-di-GMP levels and reduced swimming motility but did not affect flagellin expression or flagellar biosynthesis. After insertional mutagenesis of 12 putative genes encoding c-di-GMP metabolizing enzymes, one mutant of the locus BCAL1069 (cdpA), exhibited decreased swimming motility independent of flagellin expression in CF sputum nutritional conditions and an increase in intracellular c-di-GMP levels. The reduced swimming motility phenotype of the BCAL1069 mutant was observed in the presence of arginine and glutamate, but not of histidine, phenylalanine, or proline. The B. cenocepacia CdpA was also found to be involved in regulation of protease activity but not in biofilm formation. Altogether, these results highlight a role of B. cenocepacia BCAL1069 (CdpA) in sensing the nutritional conditions of the CF sputum and eliciting a pathogenic response that includes swimming motility toward amino acids and an increase in protease activity. FAU - Kumar, Brijesh AU - Kumar B AD - Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada. FAU - Sorensen, John L AU - Sorensen JL AD - Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada. FAU - Cardona, Silvia T AU - Cardona ST AD - Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada. AD - Department of Medical Microbiology & Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180228 PL - Switzerland TA - Front Cell Infect Microbiol JT - Frontiers in cellular and infection microbiology JID - 101585359 RN - 0 (Amino Acids) RN - 0 (Bacterial Proteins) RN - 0 (Escherichia coli Proteins) RN - 12777-81-0 (Flagellin) RN - 3KX376GY7L (Glutamic Acid) RN - 94ZLA3W45F (Arginine) RN - EC 3.1.4.- (Phosphoric Diester Hydrolases) RN - EC 3.4.- (Peptide Hydrolases) RN - EC 4.6.- (Phosphorus-Oxygen Lyases) RN - EC 4.6.1.- (diguanylate cyclase) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Amino Acid Sequence MH - Amino Acids/metabolism/pharmacology MH - Arginine/metabolism/*pharmacology MH - Bacterial Proteins/genetics/*metabolism MH - Biofilms/growth & development MH - Burkholderia Infections/microbiology MH - Burkholderia cenocepacia/*drug effects/genetics/*metabolism MH - Cloning, Molecular MH - Cyclic GMP/genetics/*metabolism MH - Cystic Fibrosis/metabolism/microbiology MH - Escherichia coli Proteins/metabolism MH - Flagellin/*biosynthesis MH - Gene Expression Regulation, Bacterial/drug effects MH - Glutamic Acid/metabolism/*pharmacology MH - Locomotion/drug effects MH - Lung/microbiology MH - Mutagenesis, Insertional MH - Peptide Hydrolases/metabolism MH - Phosphoric Diester Hydrolases/metabolism MH - Phosphorus-Oxygen Lyases/metabolism MH - Sequence Alignment MH - Sputum/chemistry PMC - PMC5835511 OTO - NOTNLM OT - BCAL1069 OT - Burkholderia cenocepacia OT - Burkholderia cepacia complex OT - SCFM OT - c-di-GMP OT - cdpA OT - cystic fibrosis OT - motility EDAT- 2018/03/16 06:00 MHDA- 2019/03/26 06:00 PMCR- 2018/01/01 CRDT- 2018/03/16 06:00 PHST- 2017/11/12 00:00 [received] PHST- 2018/02/12 00:00 [accepted] PHST- 2018/03/16 06:00 [entrez] PHST- 2018/03/16 06:00 [pubmed] PHST- 2019/03/26 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fcimb.2018.00056 [doi] PST - epublish SO - Front Cell Infect Microbiol. 2018 Feb 28;8:56. doi: 10.3389/fcimb.2018.00056. eCollection 2018.