Regulation of Virulence of Entamoeba histolytica by the URE3-BP Transcription Factor
ABSTRACTIt is not understood why only some infections withEntamoeba histolyticaresult 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 ofin vivotoin vitroparasite gene expression demonstrated that 39% ofin vivoregulated 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.IMPORTANCEAmebic dysentery and liver abscess are caused byEntamoeba histolytica. Amebae colonize the colon and cause disease by invading the intestinal epithelium. However, only one in fiveE. histolyticainfections leads to disease. The factors that govern the transition from colonization to invasion are not understood. The transcription factor upstream regulatory element 3-binding protein (URE3-BP) is a calcium-responding regulator of theE. histolyticaGal/GalNAc lectin and ferredoxin genes, both implicated in virulence. Here we discovered that inducible expression of URE3-BP changed trophozoite morphology and promoted parasite invasion in the colon and liver. These results indicate that one determinant of virulence is transcriptional regulation by URE3-BP.