Regulation of Virulence of Entamoeba histolytica by the URE3-BP Transcription Factor

• Published in: mBio 2010-05, Vol.1 (1)
• Main Authors: Gilchrist, Carol A, Moore, Ellyn S, Zhang, Yan, Bousquet, Christina B, Lannigan, Joanne A, Mann, Barbara J, Petri, William A
• Format: Article
• Language: English
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.00057-10

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.