title: MarA, SoxS and Rob function as virulence factors in an Escherichia coli murine model of ascending pyelonephritis.
abstract: MarA, SoxS and Rob are transcription factors belonging to the AraC family. While these proteins have been associated historically with control of multiple antibiotic resistance, and tolerance to oxidative stress agents and organic solvents, only a paucity of experimental data support a role in regulating virulence. Clinical Escherichia coli isolates, and isogenic strains lacking marA, soxS and rob, were studied in a murine model of ascending pyelonephritis, which is a clinically relevant model of urinary tract infection. Organisms lacking all three transcription factors (triple knockouts) were significantly less virulent than parental strains, and complementation studies demonstrated that the addition of marA, soxS and rob individually restored wild-type virulence in the triple-knockout strain. Deletion of soxS or rob alone was more detrimental than the removal of marA. Thus, all three proteins contribute to virulence in vivo.
authors.affiliation: Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Casaz
authors.affiliation: Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: Lynne K
authors.initials: LK
authors.lastname: Garrity-Ryan
authors.affiliation: Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: David
authors.initials: D
authors.lastname: McKenney
authors.affiliation: Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jackson
authors.affiliation: Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.|Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Levy
authors.affiliation: Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: S Ken
authors.initials: SK
authors.lastname: Tanaka
authors.affiliation: Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alekshun
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D051379:Mice; D011704:Pyelonephritis / Q000382:microbiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014552:Urinary Tract Infections / Q000382:microbiology; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C080002:MarA protein, E coli; C080267:Rob protein, E coli; D015534:Trans-Activators; D037521:Virulence Factors; C070725:SoxS protein, E coli