title: The pyrimidine nucleotide biosynthetic pathway modulates production of biofilm determinants in Escherichia coli.
abstract: Bacteria are often found in multicellular communities known as biofilms, which constitute a resistance form against environmental stresses. Extracellular adhesion and cell aggregation factors, responsible for bacterial biofilm formation and maintenance, are tightly regulated in response to physiological and environmental cues. We show that, in Escherichia coli, inactivation of genes belonging to the de novo uridine monophosphate (UMP) biosynthetic pathway impairs production of curli fibers and cellulose, important components of the bacterial biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus preventing production of the biofilm master regulator CsgD protein. Supplementing growth media with exogenous uracil, which can be converted to UMP through the pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli production. In addition, however, exogenous uracil triggers cellulose production, particularly in strains defective in either carB or pyrB genes, which encode enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results indicate the existence of tight and complex links between pyrimidine metabolism and curli/cellulose production: transcription of the csgDEFG operon responds to pyrimidine nucleotide availability, while cellulose production is triggered by exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate that perturbations in the UMP biosynthetic pathways allow the bacterial cell to sense signals such as starvation, nucleic acids degradation, and availability of exogenous pyrimidines, and to adapt the production of the extracellular matrix to the changing environmental conditions.
authors.affiliation: Department of Biomolecular Sciences and Biotechnology, Università degli Studi di Milano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Garavaglia
authors.forename: Elio
authors.initials: E
authors.lastname: Rossi
authors.forename: Paolo
authors.initials: P
authors.lastname: Landini
mesh_terms: D018441:Biofilms; D053898:Biosynthetic Pathways; D002482:Cellulose / Q000096:biosynthesis; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis*; D014498:Uracil / Q000494:pharmacology; D014542:Uridine Monophosphate / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D011742:Pyrimidine Nucleotides; D014498:Uracil; D002482:Cellulose; D014542:Uridine Monophosphate