title: Genome-wide transcriptional profile of Escherichia coli in response to high levels of the second messenger 3',5'-cyclic diguanylic acid.
abstract: Cyclic diguanylic acid (c-di-GMP; cGpGp) is a global second messenger controlling motility and adhesion in bacterial cells. Intracellular concentrations of c-di-GMP depend on two opposite activities: diguanylate cyclase, recently assigned to the widespread GGDEF domain, and c-di-GMP-specific phosphodiesterase, associated with proteins harboring the EAL domain. To date, little is known about the targets of c-di-GMP in the cell or if it affects transcriptional regulation of certain genes. In order to expand our knowledge of the effect of this molecule on the bacterial metabolism, here we report on the Escherichia coli transcriptional profile under high levels of c-di-GMP. We show that an important number of genes encoding cell surface and membrane-bound proteins are altered in their transcriptional activity. On the other hand, genes encoding several transcriptional factors, such as Fur, RcsA, SoxS, and ZraR, are up-regulated, and others, such as GadE, GadX, GcvA, and MetR, are down-regulated. Transcription of motility and cell division genes were altered, and consistent with this was the physiological analysis of cells overexpressing yddV, a diguanylate cyclase; these cells displayed an abnormal cell division process when high levels of c-di-GMP were present. We also show evidence that the diguanylate cyclase gene yddV is co-transcribed with dos, a heme base oxygen sensor with c-di-GMP-specific phosphodiesterase activity. A delta dos::kan mutation rendered the cells unable to divide properly, suggesting that dos and yddV may be part of a fine-tuning mechanism for regulating the intracellular levels of c-di-GMP.
authors.affiliation: Laboratorio de Microbiología y Genética Molecular, Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
authors.forename: M Marcela
authors.initials: MM
authors.lastname: Méndez-Ortiz
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hyodo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Jorge
authors.initials: J
authors.lastname: Membrillo-Hernández
mesh_terms: D001435:Bacteriophages / Q000378:metabolism; D018441:Biofilms; D002455:Cell Division; D002465:Cell Movement; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006157:Guanosine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008854:Microscopy, Electron; D008956:Models, Chemical; D008957:Models, Genetic; D016296:Mutagenesis; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; C024662:GpGp; D012313:RNA; D006157:Guanosine Monophosphate; D004247:DNA; D010100:Oxygen