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微小巴贝斯虫重组甲硫氨酸氨基肽酶蛋白:作为抗人类巴贝斯虫病疫苗候选物的免疫生化特性

Recombinant methionine aminopeptidase protein of Babesia microti: immunobiochemical characterization as a vaccine candidate against human babesiosis.

作者信息

Munkhjargal Tserendorj, Yokoyama Naoaki, Igarashi Ikuo

机构信息

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.

Institute of Veterinary Medicine, Zaisan-17042, Ulaanbaatar, Mongolia.

出版信息

Parasitol Res. 2016 Sep;115(9):3669-76. doi: 10.1007/s00436-016-5172-5. Epub 2016 Jun 15.

Abstract

Human babesiosis is the most important zoonotic protozoan infection in the world. This is the first report of the cloning, expression, purification, and immunobiochemical characterization of a methionine aminopeptidase 1 (MetAP1) protein from Babesia microti (B. microti). The gene encodes a MetAP1 protein of B. microti (BmMetAP1) of approximately 66.8 kDa that includes glutathione S-transferase (GST) tag and shows MetAP activity. BmMetAP1 was detected in a lysate of B. microti and further localized in cytoplasm of the B. microti merozoite. rBmMetAP1 was found to be immunogenic, eliciting a high antibody titer in mice. Moreover, rBmMetAP1 stimulated the production of IFN-γ and IL-12 but not IL-4. Finally, rBmMetAP1 was able to provide considerable protection to mice against a B. microti challenge infection based on a reduction in peak parasitemia levels and earlier clearance of the parasite as compared with control mice. Taken together, these results suggest that rBmMetAP1 confers significant protection against experimental B. microti infection and might be considered a potential vaccine target against human babesiosis.

摘要

人巴贝斯虫病是世界上最重要的人畜共患原生动物感染病。这是关于微小巴贝斯虫(B. microti)甲硫氨酸氨肽酶1(MetAP1)蛋白的克隆、表达、纯化及免疫生化特性的首次报道。该基因编码一种约66.8 kDa的微小巴贝斯虫MetAP1蛋白(BmMetAP1),其包含谷胱甘肽S-转移酶(GST)标签并具有MetAP活性。在微小巴贝斯虫裂解物中检测到BmMetAP1,并进一步定位在微小巴贝斯虫裂殖子的细胞质中。发现重组BmMetAP1(rBmMetAP1)具有免疫原性,可在小鼠中引发高抗体滴度。此外,rBmMetAP1刺激了IFN-γ和IL-12的产生,但未刺激IL-4的产生。最后,与对照小鼠相比,rBmMetAP1能够基于峰值寄生虫血症水平的降低和寄生虫的更早清除,为小鼠提供相当程度的保护,使其免受微小巴贝斯虫攻击感染。综上所述,这些结果表明rBmMetAP1对实验性微小巴贝斯虫感染具有显著保护作用,可能被视为抗人巴贝斯虫病的潜在疫苗靶点。

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