title: Constitutive production of c-di-GMP is associated with mutations in a variant of Pseudomonas aeruginosa with altered membrane composition.
abstract: 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.
authors: 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.
authors: Andrea
authors: A
authors: Blanka
authors: 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.
authors: Juliane
authors: J
authors: Düvel
authors: 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.
authors: Andreas
authors: A
authors: Dötsch
authors: Microbial Biology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Birgit
authors: B
authors: Klinkert
authors: Department of Chemical Microbiology, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
authors: Wolf-Rainer
authors: WR
authors: Abraham
authors: Research Core Unit Metabolomics and Institute of Pharmacology, Hannover Medical School, 30625 Hannover, Germany.
authors: Volkhard
authors: V
authors: Kaever
authors: Department of Macromolecular Interactions, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
authors: Christiane
authors: C
authors: Ritter
authors: Microbial Biology, Ruhr University Bochum, 44801 Bochum, Germany.
authors: Franz
authors: F
authors: Narberhaus
authors: 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.
authors: Susanne
authors: S
authors: Häussler
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D018441:Biofilms; D002462:Cell Membrane / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000096:biosynthesis; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics; D009154:Mutation; D009690:Nucleic Acid Conformation; D010641:Phenotype; D014176:Protein Biosynthesis / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D020121:5' Untranslated Regions; D001426:Bacterial Proteins; D005227:Fatty Acids; D012333:RNA, Messenger; D012965:Sodium Chloride; C062025:bis(3',5')-cyclic diguanylic acid; D000103:Acetyl-CoA Carboxylase; D006152:Cyclic GMP