Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor
Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor
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DOI：
10.1016/s0166-6851(01)00432-7
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发表时间：
2002-03-01
影响因子：
1.5
通讯作者：
McMaster, WR
中科院分区：
文献类型：
--
作者：
Joshi, PB;Kelly, BL;McMaster, WR
利什曼溶血素，63 kDa的利什曼原虫表面金属蛋白酶（GP 63）已被描述为寄生虫毒力因子，并参与前鞭毛体和宿主巨噬细胞受体的直接相互作用以及与补体级联的相互作用。为了研究利什曼溶血素在硕大利什曼原虫致病性和毒力中的作用，使用靶向基因置换来删除包含所有7个利什曼溶血素基因（gp 63基因1-7）的整个20 kb区域。由此产生的L。主要的利什曼溶血素缺陷突变体在白蛉载体内显示正常发育，然而，从白蛉或培养物中回收的前鞭毛体显示对补体介导的裂解的敏感性增加，并且在BALB/c动物中损伤形成延迟。克隆的利什曼溶血素基因的表达可以显着改善表型差异。这些结果表明，利什曼溶血素是一个重要的毒力因子在利什曼原虫的发病机制。(C)2002 Elsevier Science B. V.保留所有权利。
Leishmanolysin, the Leishmania surface metalloproteinase of 63 kDa (GP63) has been described as a parasite virulence factor and is involved in the direct interaction of promastigotes and host macrophage receptors and interaction with the complement cascade. To study the role of leishmanolysin in the pathogenesis and virulence of Leishmania major, targeted gene replacement was used to delete the entire 20 kb region containing all seven leishmanolysin genes (gp63 genes 1-7). The resulting L. major leishmanolysin deficient mutants showed normal development inside the sand fly vector, however, promastigotes recovered from sand flies or from culture showed an increase in sensitivity to complement-mediated lysis and a delay in lesion formation in BALB/c animals. The phenotypic differences could be significantly improved by expression of a cloned leishmanolysin gene. These results demonstrate that leishmanolysin is a vital virulence factor in Leishmania pathogenesis. (C) 2002 Elsevier Science B.V. All rights reserved.