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大丽轮枝菌糖基化突变体在适宜的沙蝇媒介中生存需要磷酸糖脂(lpg2-),但不需要脂磷糖脂(lpg1-)。

Leishmania major glycosylation mutants require phosphoglycans (lpg2-) but not lipophosphoglycan (lpg1-) for survival in permissive sand fly vectors.

机构信息

Department of Parasitology, Faculty of Science, Charles University in Prague, Czech Republic.

出版信息

PLoS Negl Trop Dis. 2010 Jan 12;4(1):e580. doi: 10.1371/journal.pntd.0000580.

DOI:10.1371/journal.pntd.0000580
PMID:20084096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2797086/
Abstract

BACKGROUND

Sand fly species able to support the survival of the protozoan parasite Leishmania have been classified as permissive or specific, based upon their ability to support a wide or limited range of strains and/or species. Studies of a limited number of fly/parasite species combinations have implicated parasite surface molecules in this process and here we provide further evidence in support of this proposal. We investigated the role of lipophosphoglycan (LPG) and other phosphoglycans (PGs) in sand fly survival, using Leishmania major mutants deficient in LPG (lpg1(-)), and the phosphoglycan (PG)-deficient mutant lpg2(-). The sand fly species used were the permissive species Phlebotomus perniciosus and P. argentipes, and the specific vector P. duboscqi, a species resistant to L. infantum development.

PRINCIPAL FINDINGS

The lpg2(-) mutants did not survive well in any of the three sand fly species, suggesting that phosphoglycans and/or other LPG2-dependent molecules are required for parasite development. In vitro, all three L. major lines were equally resistant to proteolytic activity of bovine trypsin, suggesting that sand fly-specific hydrolytic proteases or other factors are the reason for the early lpg2(-) parasite killing. The lpg1(-) mutants developed late-stage infections in two permissive species, P. perniciosus and P. argentipes, where their infection rates and intensities of infections were comparable to the wild type (WT) parasites. In contrast, in P. duboscqi the lpg1(-) mutants developed significantly worse than the WT parasites.

CONCLUSIONS

In combination with previous studies, the data establish clearly that LPG is not required for Leishmania survival in permissive species P. perniciosus and P. argentipes but plays an important role in the specific vector P. duboscqi. With regard to PGs other than LPG, the data prove the importance of LPG2-related molecules for survival of L. major in the three sand fly species tested.

摘要

背景

根据沙蝇物种对原生动物寄生虫利什曼原虫生存的支持能力,可将其分为允许或特定的物种,这取决于它们支持广泛或有限范围的菌株和/或物种的能力。对有限数量的蝇/寄生虫物种组合的研究表明,寄生虫表面分子在这个过程中起作用,在这里我们提供了进一步支持这一建议的证据。我们研究了脂磷甘露聚糖(LPG)和其他磷酸甘露聚糖(PG)在沙蝇生存中的作用,使用利什曼原虫 lpg1(-)缺陷突变体和磷酸甘露聚糖(PG)缺陷突变体 lpg2(-)。所用的沙蝇物种是允许的物种珀氏白蛉和 P. argentipes,以及特定的载体 P. duboscqi,这是一种对 L. infantum 发育有抗性的物种。

主要发现

lpg2(-)突变体在这三种沙蝇中都不能很好地存活,这表明磷酸甘露聚糖和/或其他依赖 LPG2 的分子是寄生虫发育所必需的。在体外,所有三种利什曼原虫株都对牛胰蛋白酶的蛋白水解活性具有同等的抗性,这表明沙蝇特异性的水解蛋白酶或其他因素是导致早期 lpg2(-)寄生虫死亡的原因。lpg1(-)突变体在两种允许的物种珀氏白蛉和 P. argentipes 中发展为晚期感染,其感染率和感染强度与野生型(WT)寄生虫相当。相比之下,在 P. duboscqi 中,lpg1(-)突变体的发育明显比 WT 寄生虫差。

结论

结合以前的研究,数据清楚地表明,LPG 不是利什曼原虫在允许的物种珀氏白蛉和 P. argentipes 中生存所必需的,但在特定的载体 P. duboscqi 中起着重要的作用。关于除 LPG 以外的 PG,数据证明了 LPG2 相关分子对三种测试的沙蝇物种中利什曼原虫生存的重要性。

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