Department of Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
mBio. 2010 May 18;1(1):e00057-10. 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.
目前尚不清楚为什么只有某些溶组织内阿米巴感染会导致疾病。钙调节转录因子上游调节元件结合蛋白（URE3-BP）最初是因其在调节两种阿米巴毒力基因（Gal/GalNac 凝集素和铁氧还蛋白）表达中的作用而被鉴定的。在这里，我们测试了这种转录因子是否在调节毒力方面具有更广泛的作用。体内与体外寄生虫基因表达的比较表明，与所有启动子的 23%相比，39%的体内调节转录本含有 URE3-BP 识别的 URE3 基序（P < 0.0001）。诱导表达显性阳性突变形式的 URE3-BP 的变形虫具有伸长形态的增加（30% +/- 6%比 14% +/- 5%；P = 0.001），在侵袭肠上皮方面具有 2 倍的竞争优势（P = 0.017），并且肝脓肿大小增加了 3 倍（0.1 +/- 0.1 g 比 0.036 +/- 0.1 g；P = 0.03）。这些结果支持 URE3-BP 在毒力调节中的作用。
