Wiśniewski Marcin, Jaros Sławomir, Bąska Piotr, Cappello Michael, Długosz Ewa, Wędrychowicz Halina
Division of Parasitology and Parasitic Diseases, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, 02-0787 Warsaw, Ciszewskiego 8, Poland.
Division of Pharmacology and Toxicology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, 02-0787 Warsaw, Ciszewskiego 8, Poland.
Exp Parasitol. 2016 Apr;163:1-7. doi: 10.1016/j.exppara.2016.01.006. Epub 2016 Jan 18.
Hookworms are intestinal nematodes that infect up to 740 million people, mostly in tropical and subtropical regions. Adult worms suck blood from damaged vessels in the gut mucosa, digesting hemoglobin using aspartic-, cysteine- and metalloproteases. Targeting aspartic hemoglobinases using drugs or vaccines is therefore a promising approach to ancylostomiasis control. Based on homology to metalloproteases from other hookworm species, we cloned the Ancylostoma ceylanicum metalloprotease 7 cDNA (Ace-mep-7). The corresponding Ace-MEP-7 protein has a predicted molecular mass of 98.8 kDa. The homology to metallopeptidases from other hookworm species and its predicted transmembrane region support the hypothesis that Ace-MEP-7 may be involved in hemoglobin digestion in the hookworm gastrointestinal tract, especially that our analyses show expression of Ace-mep-7 in the adult stage of the parasite. Immunization of Syrian golden hamsters with Ace-mep-7 cDNA resulted in 50% (p < 0.01) intestinal worm burden reduction. Additionally 78% (p < 0.05) egg count reduction in both sexes was observed. These results suggest that immunization with Ace-mep-7 may contribute to reduction in egg count released into the environment during the A. ceylanicum infection.
钩虫是肠道线虫，感染人数多达7.4亿，主要分布在热带和亚热带地区。成虫从肠道黏膜受损血管中吸血，利用天冬氨酸蛋白酶、半胱氨酸蛋白酶和金属蛋白酶消化血红蛋白。因此，使用药物或疫苗靶向天冬氨酸血红蛋白酶是控制钩虫病的一种有前景的方法。基于与其他钩虫物种金属蛋白酶的同源性，我们克隆了锡兰钩虫金属蛋白酶7 cDNA（Ace-mep-7）。相应的Ace-MEP-7蛋白预测分子量为98.8 kDa。与其他钩虫物种金属肽酶的同源性及其预测的跨膜区域支持了Ace-MEP-7可能参与钩虫胃肠道血红蛋白消化的假说，特别是我们的分析表明Ace-mep-7在寄生虫成虫阶段表达。用Ace-mep-7 cDNA免疫叙利亚金仓鼠可使肠道蠕虫负荷降低50%（p<0.01）。此外，观察到两性的虫卵计数均减少78%（p<0.05）。这些结果表明，用Ace-mep-7免疫可能有助于减少锡兰钩虫感染期间释放到环境中的虫卵数量。
