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致病性钩端螺旋体属种外膜脂蛋白编码基因 ompL1、UpL32 和 lipL41 的进化意义。

Evolutionary implication of outer membrane lipoprotein-encoding genes ompL1, UpL32 and lipL41 of pathogenic Leptospira species.

机构信息

Division of Medical Microbiology, Department of Microbiology, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, Tamilnadu, India.

出版信息

Genomics Proteomics Bioinformatics. 2009 Sep;7(3):96-106. doi: 10.1016/S1672-0229(08)60038-8.

Abstract

Leptospirosis is recognized as the most widespread zoonosis with a global distribution. In this study, the antigenic variation in Leptospira interrogans and Leptospira borgpetersenii isolated from human urine and field rat kidney was preliminarily confirmed by microscopic agglutination test using monoclonal antibodies, and was further subjected to amplification and identification of outer membrane lipoproteins with structural gene variation. Sequence similarity analysis revealed that these protein sequences, namely OmpL1, LipL32 and LipL41, showed no more homologies to outer membrane lipoproteins of non-pathogenic Leptospira and other closely related Spirochetes, but showed a strong identity within L. interrogans, suggesting intra-specific phylogenetic lineages that might be originated from a common pathogenic leptospiral origin. Moreover, the ompL1 gene showed more antigenic variation than UpL32 and lipL41 due to less conservation in secondary structural evolution within closely related species. Phylogenetically, ompLl and lipL41 of these strains gave a considerable proximity to L. weilii and L. santaro-sai. The ompLl gene of L. interrogans clustered distinctly from other pathogenic and non-pathogenic leptospiral species. The diversity of ompL genes has been analyzed and it envisaged that sequence-specific variations at antigenic determinant sites would result in slow evolutionary changes along with new serovar origination within closely related species. Thus, a crucial work on effective recombinant vaccine development and engineered antibodies will hopefully meet to solve the therapeutic challenges.

摘要

钩端螺旋体病被认为是分布最广泛的人畜共患病。在这项研究中,通过使用单克隆抗体的显微镜凝集试验初步证实了从人尿和野鼠肾中分离出的问号钩端螺旋体和伯氏包柔螺旋体的抗原变异,并进一步扩增和鉴定了具有结构基因变异的外膜脂蛋白。序列相似性分析表明,这些蛋白质序列,即 OmpL1、LipL32 和 LipL41,与非致病性钩端螺旋体和其他密切相关的螺旋体的外膜脂蛋白没有更多的同源性,但在问号钩端螺旋体内部表现出很强的同一性,表明可能来自共同的致病性钩端螺旋体起源的种内系统发育谱系。此外,由于在密切相关的物种中二级结构进化中较少保守,ompL1 基因比 UpL32 和 lipL41 表现出更多的抗原变异。从系统发育上看,这些菌株的 ompLl 和 lipL41 与利氏钩端螺旋体和圣塔-索尼钩端螺旋体非常接近。问号钩端螺旋体的 ompLl 基因明显与其他致病性和非致病性钩端螺旋体物种聚类。对 ompL 基因的多样性进行了分析,预计抗原决定簇位点的序列特异性变异将导致沿着密切相关物种中新血清型起源的缓慢进化变化。因此,在有效重组疫苗开发和工程抗体方面的重要工作有望解决治疗挑战。

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