title: Lrp-DNA complex stability determines the level of ON cells in type P fimbriae phase variation.
abstract: F165(1) and the pyelonephritis-associated pili (Pap) are two members of the type P family of adhesive factors that play a key role in the establishment of disease caused by extraintestinal Escherichia coli (ExPEC) strains. They are both under the control of an epigenetic and reversible switch that defines the number of fimbriated (ON) and afimbriated (OFF) cells within a clonal population. Our present study demonstrates that the high level of ON cells found during F165(1) phase variation is due to altered stability of the DNA complex formed by the leucine-responsive regulatory protein (Lrp) at its repressor binding sites 1-3; after each cell cycle, complex formation is also modulated by the local regulator FooI (homologue to PapI) which promotes the transit of Lrp towards its activator binding sites 4-6. Furthermore, we identified two nucleotides (T490, G508) surrounding the Lrp binding site 1 that are critical to maintaining a high OFF to ON switch rate during F165(1) phase variation, as well as switching Pap fimbriae towards the OFF state.
authors.affiliation: Groupe de Recherche sur les Maladies Infectieuses du Porc and Centre de Recherche en Infectiologie Porcine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Graveline
authors.forename: Michaël
authors.initials: M
authors.lastname: Mourez
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hancock
authors.forename: Christine
authors.initials: C
authors.lastname: Martin
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisclair
authors.forename: Josée
authors.initials: J
authors.lastname: Harel
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002453:Cell Cycle; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000096:biosynthesis / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D051756:Leucine-Responsive Regulatory Protein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C088773:F165 protein, E coli; C497278:Lrp protein, E coli; D051756:Leucine-Responsive Regulatory Protein; D036781:Fimbriae Proteins