title: Regulation of Virulence of Entamoeba histolytica by the URE3-BP Transcription Factor.
abstract: It is not understood why only some infections with Entamoeba histolytica result in disease. The calcium-regulated transcription factor upstream regulatory element 3-binding protein (URE3-BP) was initially identified by virtue of its role in regulating the expression of two amebic virulence genes, the Gal/GalNac lectin and ferredoxin. Here we tested whether this transcription factor has a broader role in regulating virulence. A comparison of in vivo to in vitro parasite gene expression demonstrated that 39% of in vivo regulated transcripts contained the URE3 motif recognized by URE3-BP, compared to 23% of all promoters (P < 0.0001). Amebae induced to express a dominant positive mutant form of URE3-BP had an increase in an elongated morphology (30% +/- 6% versus 14% +/- 5%; P = 0.001), a 2-fold competitive advantage at invading the intestinal epithelium (P = 0.017), and a 3-fold increase in liver abscess size (0.1 +/- 0.1 g versus 0.036 +/- 0.1 g; P = 0.03). These results support a role for URE3-BP in virulence regulation.
authors.affiliation: Department of Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gilchrist
authors.forename: Ellyn S
authors.initials: ES
authors.lastname: Moore
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Christina B
authors.initials: CB
authors.lastname: Bousquet
authors.forename: Joanne A
authors.initials: JA
authors.lastname: Lannigan
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Mann
authors.forename: William A
authors.initials: WA
authors.lastname: Petri