PMID- 25872871 OWN - NLM STAT- MEDLINE DCOM- 20160115 LR - 20160513 IS - 1937-9145 (Electronic) IS - 1945-0877 (Linking) VI - 8 IP - 372 DP - 2015 Apr 14 TI - Constitutive production of c-di-GMP is associated with mutations in a variant of Pseudomonas aeruginosa with altered membrane composition. PG - ra36 LID - 10.1126/scisignal.2005943 [doi] AB - Most bacteria can form multicellular communities called biofilms on biotic and abiotic surfaces. This multicellular response to surface contact correlates with an increased resistance to various adverse environmental conditions, including those encountered during infections of the human host and exposure to antimicrobial compounds. Biofilm formation occurs when freely swimming (planktonic) cells encounter a surface, which stimulates the chemosensory-like, surface-sensing system Wsp and leads to generation of the intracellular second messenger 3',5'-cyclic-di-guanosine monophosphate (c-di-GMP). We identified adaptive mutations in a clinical small colony variant (SCV) of Pseudomonas aeruginosa and correlated their presence with self-aggregating growth behavior and an enhanced capacity to form biofilms. We present evidence that a point mutation in the 5' untranslated region of the accBC gene cluster, which encodes components of an enzyme responsible for fatty acid biosynthesis, was responsible for a stabilized mRNA structure that resulted in reduced translational efficiency and an increase in the proportion of short-chain fatty acids in the plasma membrane. We propose a model in which these changes in P. aeruginosa serve as a signal for the Wsp system to constitutively produce increased amounts of c-di-GMP and thus play a role in the regulation of adhesion-stimulated bacterial responses. CI - Copyright (c) 2015, American Association for the Advancement of Science. FAU - Blanka, Andrea AU - Blanka A AD - Institute for Molecular Bacteriology, TWINCORE GmbH, Center of Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30625 Hannover, Germany. FAU - Duvel, Juliane AU - Duvel J AD - Institute for Molecular Bacteriology, TWINCORE GmbH, Center of Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30625 Hannover, Germany. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany. FAU - Dotsch, Andreas AU - Dotsch A AD - Institute for Molecular Bacteriology, TWINCORE GmbH, Center of Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30625 Hannover, Germany. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany. FAU - Klinkert, Birgit AU - Klinkert B AD - Microbial Biology, Ruhr University Bochum, 44801 Bochum, Germany. FAU - Abraham, Wolf-Rainer AU - Abraham WR AD - Department of Chemical Microbiology, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany. FAU - Kaever, Volkhard AU - Kaever V AD - Research Core Unit Metabolomics and Institute of Pharmacology, Hannover Medical School, 30625 Hannover, Germany. FAU - Ritter, Christiane AU - Ritter C AD - Department of Macromolecular Interactions, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany. FAU - Narberhaus, Franz AU - Narberhaus F AD - Microbial Biology, Ruhr University Bochum, 44801 Bochum, Germany. FAU - Haussler, Susanne AU - Haussler S AD - Institute for Molecular Bacteriology, TWINCORE GmbH, Center of Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Center for Infection Research, 30625 Hannover, Germany. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany. susanne.haeussler@twincore.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150414 PL - United States TA - Sci Signal JT - Science signaling JID - 101465400 RN - 0 (5' Untranslated Regions) RN - 0 (Bacterial Proteins) RN - 0 (Fatty Acids) RN - 0 (RNA, Messenger) RN - 451W47IQ8X (Sodium Chloride) RN - 61093-23-0 (bis(3',5')-cyclic diguanylic acid) RN - EC 6.4.1.2 (Acetyl-CoA Carboxylase) RN - H2D2X058MU (Cyclic GMP) SB - IM MH - 5' Untranslated Regions/genetics MH - Acetyl-CoA Carboxylase/genetics/metabolism MH - Bacterial Proteins/genetics/metabolism MH - Base Sequence MH - Biofilms MH - Cell Membrane/*metabolism MH - Cyclic GMP/*analogs & derivatives/biosynthesis MH - Cytosol/drug effects/metabolism MH - Fatty Acids/metabolism MH - Multigene Family/genetics MH - *Mutation MH - Nucleic Acid Conformation MH - Phenotype MH - Protein Biosynthesis/genetics MH - Pseudomonas aeruginosa/*genetics/*metabolism/physiology MH - RNA, Messenger/chemistry/genetics/metabolism MH - Sequence Homology, Nucleic Acid MH - Signal Transduction/drug effects/genetics MH - Sodium Chloride/pharmacology EDAT- 2015/04/16 06:00 MHDA- 2016/01/16 06:00 CRDT- 2015/04/16 06:00 PHST- 2015/04/16 06:00 [entrez] PHST- 2015/04/16 06:00 [pubmed] PHST- 2016/01/16 06:00 [medline] AID - 8/372/ra36 [pii] AID - 10.1126/scisignal.2005943 [doi] PST - epublish SO - Sci Signal. 2015 Apr 14;8(372):ra36. doi: 10.1126/scisignal.2005943.