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首页> 外文期刊>Infection and immunity >A Recombinant β-1,3-Glucanosyltransferase Homolog of Coccidioides posadasii Protects Mice against Coccidioidomycosis
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A Recombinant β-1,3-Glucanosyltransferase Homolog of Coccidioides posadasii Protects Mice against Coccidioidomycosis

机译：球孢子虫的重组β-1,3-葡糖基转移酶同系物可保护小鼠免于球孢子菌病

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Coccidioides posadasii is a fungal respiratory pathogen which is responsible for recurrent epidemics of San Joaquin Valley fever (coccidioidomycosis) in desert regions of the southwestern United States. Numerous studies have revealed that the cell wall of the parasitic phase of the fungus is a reservoir of immunoreactive macromolecules and a potential source of a vaccine against this mycosis. A 495-bp fragment of a C. posadasii gene which encodes a putative wall-associated, glycosylphosphatidylinositol (GPI)-anchored β-1,3-glucanosyltransferase was identified by computational analysis of the partially sequenced genome of this pathogen. The translated, full-length gene (GEL1) showed high sequence homology to a reported β-1,3-glucanosyltransferase of Aspergillus fumigatus (70% identity, 90% similarity) and was selected for further study. The GEL1 mRNA of C. posadasii was detected at the highest level during the endosporulation stage of the parasitic cycle, and the mature protein was immunolocalized to the surface of endospores. BALB/c or C57BL/6 mice were immunized subcutaneously with the bacterium-expressed recombinant protein (rGel1p) to evaluate its protective efficacy against a lethal challenge of C. posadasii by either the intraperitoneal or intranasal route. In both cases, rGel1p-immune mice infected with the pathogen showed a significant reduction in fungal burden and increased survival compared to nonimmune mice. The recombinant β-1,3-glucanosyltransferase is a valuable addition to an arsenal of immunoreactive proteins which could be incorporated into a human vaccine against coccidioidomycosis.
机译： Coccidioides posadasii 是一种真菌性呼吸道病原体，是导致美国西南部沙漠地区圣华金山谷热（球孢子菌病）反复流行的原因。大量研究表明，真菌寄生期的细胞壁是免疫反应性大分子的贮藏库，也是抗这种真菌病的疫苗的潜在来源。 C的495 bp片段。通过对这种病原体的部分测序基因组进行计算分析，确定了编码假定的与壁相关的糖基磷脂酰肌醇（GPI）锚定的β-1,3-葡糖基转移酶的posadasii基因。已翻译的全长基因（ GEL1 ）与报道的 fumigatus 的β-1,3-葡糖基转移酶具有高度序列同源性（70％相同，90％相似）。并被选作进一步研究。 C的 GEL1 mRNA。在寄生周期的内孢子形成阶段以最高水平检测到了posadasii ，并且将成熟蛋白免疫定位在了内生孢子的表面。用细菌表达的重组蛋白（rGel1p）皮下免疫BALB / c或C57BL / 6小鼠，以评估其对 C致死性攻击的保护作用。 posadasii 的腹膜内或鼻内途径。在这两种情况下，与非免疫小鼠相比，感染病原体的rGel1p免疫小鼠均表现出真菌负担的显着减少和存活率的提高。重组β-1，3-葡糖基糖基转移酶是免疫反应蛋白库的重要补充，可将其掺入抗球虫病的人疫苗中。

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