Regulation of Virulence of Entamoeba histolytica by the URE3-BP Transcription Factor
| Autor: | Joanne A. Lannigan, Christina B. Bousquet, Carol A. Gilchrist, Ellyn S. Moore, Barbara J. Mann, William A. Petri, Yan Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
0303 health sciences
biology 030306 microbiology Virulence Promoter biology.organism_classification Microbiology QR1-502 3. Good health 03 medical and health sciences Entamoeba histolytica Intestinal mucosa Virology Gene expression parasitic diseases Transcriptional regulation Gene Transcription factor 030304 developmental biology Research Article |
| Zdroj: | mBio, Vol 1, Iss 1 (2010) mBio |
| ISSN: | 2150-7511 |
| DOI: | 10.1128/mBio.00057-10 |
| Popis: | 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. IMPORTANCE Amebic dysentery and liver abscess are caused by Entamoeba histolytica. Amebae colonize the colon and cause disease by invading the intestinal epithelium. However, only one in five E. histolytica infections 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 the E. histolytica Gal/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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|