Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, SY23 2DA, UK.
J Proteome Res. 2012 Dec 7;11(12):5876-89. doi: 10.1021/pr300654w. Epub 2012 Nov 28.
Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member.
片形吸虫病是一种重要的食源性人畜共患疾病,全球每年因此造成的健康和经济损失估计达数十亿美元。肝片形吸虫是温带地区的主要种,而巨片形吸虫则在热带地区占主导地位。由于目前尚无商业可用的疫苗来控制片形吸虫病,加之对现有化疗策略的耐药性不断增加以及片形吸虫病传播到新的地区,因此正在采用新的功能基因组学方法来鉴定潜在的新药物靶点和疫苗候选物。谷胱甘肽转移酶(GST)超家族既是候选药物也是疫苗靶点。本研究鉴定了一种来自热带肝片形吸虫的水溶性胞质提取物中的假定新型 Sigma 类 GST。该 GST 被克隆并表达为具有酶活性的重组蛋白。与目前处于 II 期临床试验阶段的人类血吸虫病 GST 疫苗相比,该 GST 与先前发现的巨片形吸虫 GST 具有更高的同源性,这激发了人们对其免疫保护特性的兴趣。此外,对巨片形吸虫和肝片形吸虫 GST 超家族的计算机分析揭示了一个额外的 Mu 类 GST、Omega 类 GST,以及首次发现的一个 Zeta 类成员。