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通过杜氏利什曼原虫突变体的功能互补鉴定介导脂磷酸聚糖生物合成的基因。

Identification of genes mediating lipophosphoglycan biosynthesis by functional complementation of Leishmania donovani mutants.

作者信息

Beverley S M, Turco S J

机构信息

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Ann Trop Med Parasitol. 1995 Dec;89 Suppl 1:11-17. doi: 10.1080/00034983.1995.11813009.

DOI:10.1080/00034983.1995.11813009
PMID:8745922
Abstract

A powerful approach for identifying the genes involved in the infectious cycle of pathogens is functional genetic complementation. Here, the current status of this technology in Leishmania is reviewed, focusing on the genes involved in the biosynthesis of the unique parasite surface glycolipid, lipophosphoglycan (LPG). LPG plays multiple roles in the Leishmania infectious cycle, in both the sand fly vector and in establishing successful intracellular parasitism within the vertebrate macrophage. The emerging methods for generating LPG mutations and for recovering the affected gene(s) by complementation with an episomal genomic Leishmania DNA library are reviewed. The properties and probable roles of the first two genes identified by this methodology are discussed. These methods also show great promise in the search for genes affecting other virulence factors of Leishmania as well as in the identification of new drug-resistance loci.

摘要

一种用于鉴定参与病原体感染周期的基因的强大方法是功能基因互补。本文综述了该技术在利什曼原虫中的现状,重点关注参与独特寄生虫表面糖脂——脂磷壁酸(LPG)生物合成的基因。LPG在利什曼原虫的感染周期中发挥多种作用,包括在沙蝇载体中以及在脊椎动物巨噬细胞内建立成功的细胞内寄生。本文综述了产生LPG突变以及通过与附加体质粒基因组利什曼原虫DNA文库互补来恢复受影响基因的新出现的方法。讨论了通过这种方法鉴定出的前两个基因的特性和可能的作用。这些方法在寻找影响利什曼原虫其他毒力因子的基因以及鉴定新的耐药位点方面也显示出巨大的前景。

相似文献

1
Identification of genes mediating lipophosphoglycan biosynthesis by functional complementation of Leishmania donovani mutants.通过杜氏利什曼原虫突变体的功能互补鉴定介导脂磷酸聚糖生物合成的基因。
Ann Trop Med Parasitol. 1995 Dec;89 Suppl 1:11-17. doi: 10.1080/00034983.1995.11813009.
2
A specialized pathway affecting virulence glycoconjugates of Leishmania.一条影响利什曼原虫毒力糖缀合物的特殊途径。
Science. 1995 Sep 29;269(5232):1869-72. doi: 10.1126/science.7569927.
3
Lipophosphoglycan (LPG) and the identification of virulence genes in the protozoan parasite Leishmania.脂磷壁酸聚糖(LPG)与原生动物寄生虫利什曼原虫毒力基因的鉴定。
Trends Microbiol. 1998 Jan;6(1):35-40. doi: 10.1016/S0966-842X(97)01180-3.
4
Leishmania LPG3 encodes a GRP94 homolog required for phosphoglycan synthesis implicated in parasite virulence but not viability.利什曼原虫LPG3编码一种GRP94同源物,该同源物是磷酸聚糖合成所必需的,与寄生虫毒力有关,但与生存能力无关。
EMBO J. 2002 Sep 2;21(17):4458-69. doi: 10.1093/emboj/cdf447.
5
Reduced expression of lipophosphoglycan (LPG) and kinetoplastid membrane protein (KMP)-11 in Leishmania donovani promastigotes in axenic culture.体外培养的杜氏利什曼原虫前鞭毛体中脂磷壁酸聚糖(LPG)和动基体膜蛋白(KMP)-11的表达降低。
J Parasitol. 1998 Jun;84(3):644-7.
6
Isolation of virulence genes directing surface glycosyl-phosphatidylinositol synthesis by functional complementation of Leishmania.通过利什曼原虫的功能互补分离指导表面糖基磷脂酰肌醇合成的毒力基因。
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8609-13. doi: 10.1073/pnas.90.18.8609.
7
Leishmania donovani has distinct mannosylphosphoryltransferases for the initiation and elongation phases of lipophosphoglycan repeating unit biosynthesis.杜氏利什曼原虫在脂磷酸聚糖重复单元生物合成的起始和延伸阶段具有不同的甘露糖基磷酸转移酶。
Mol Biochem Parasitol. 1998 Jul 1;94(1):27-40. doi: 10.1016/s0166-6851(98)00047-4.
8
Kinetics of entry of virulent and avirulent strains of Leishmania donovani into macrophages: a possible role of virulence molecules (gp63 and LPG).杜氏利什曼原虫强毒株和无毒株进入巨噬细胞的动力学:毒力分子(gp63和脂磷壁酸)的可能作用
J Parasitol. 1996 Aug;82(4):632-5.
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Leishmania lipophosphoglycan activates the transcription factor activating protein 1 in J774A.1 macrophages through the extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase.利什曼原虫脂磷壁酸通过细胞外信号调节激酶(ERK)和p38丝裂原活化蛋白激酶激活J774A.1巨噬细胞中的转录因子活化蛋白1。
Mol Biochem Parasitol. 2005 Jan;139(1):117-27. doi: 10.1016/j.molbiopara.2004.10.006.
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Characterization of the glucosyltransferases that assemble the side chains of the Indian Leishmania donovani lipophosphoglycan.组装杜氏利什曼原虫脂磷酸聚糖侧链的葡糖基转移酶的特性分析
Arch Biochem Biophys. 1999 Dec 15;372(2):367-74. doi: 10.1006/abbi.1999.1531.

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