DEVELOPMENTAL BIOLOGY OF LEISHMANIA PROMASTIGOTES
利什曼原虫前鞭毛体的发育生物学
基本信息
- 批准号:3746490
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
The life-cycle of Leishmania parasites within the sand fly vector
includes the development of extracellular promastigotes from a
noninfective, procyclic stage into an infective, metacyclic stage.
These adaptations were explored in the context of the structure and
function of the abundant surface lipophosphoglycan (LPG) on Leishmania
donovani promastigotes. During metacyclogenesis, two important
developmental modifications were observed. First, the size of the
molecule is substantially increased due to a 2-fold increase in the
number of phosphorylated disaccharide repeat units expressed.
Second, there is a concomitant decrease in the presentation of
terminally exposed sugars. The capping sugars on procyclic LPG were
found to mediate procyclic attachment to the sand fly midgut, whereas
these same sugars on metacyclic LPG failed to mediate metacyclic
binding. And whereas intact metacyclic LPG did not inhibit procyclic
attachment, depolymerized LPG inhibited as well as procyclic LPG,
demonstrating that the ligands are normally buried. The exposure and
subsequent masking of the terminal capping sugars explains the stage-
specificity of promastigote attachment to and release from the vector
midgut, which are key events in the development of transmissible
infections in the fly.
Phlebotomine vectors are in some instances able to transmit only
certain species of Leishmania. Comparison of a large number of
vector/parasite pairs revealed that species-specific differences in
vectorial competence were in every case directly correlated with the
ability of promastigotes to attach to the sand fly midgut, the
variable outcomes of which were controlled by structural polymorphisms
in the surface lipophosphoglycan (LPG) of the parasite. The data
suggest that at least some phlebotomine vectors differ with respect to
the parasite recognition sites which they express, and that midgut
adhesion is a sufficiently critical component of vectorial competence
as to provide the evolutionary drive for LPG structural polymorphisms.
Mutants defective in expression of specific sugars involved in midgut
attachment have been selected using lectins or antibodies which bind
to the functional domains on LPG. LPG mutants have been obtained
which fail to bind to the midgut or survive in the fly, and we are
attempting to recover the defective genes by functional
complementation.
沙蝇媒介中利什曼原虫寄生虫的生命周期
包括细胞外前鞭毛体的发育
非感染性、前循环阶段转变为感染性、后循环阶段。
这些调整是在结构和结构的背景下进行探索的。
丰富的表面脂磷酸聚糖(LPG)对利什曼原虫的作用
多诺瓦尼前鞭毛体。 在后生轮发生过程中,有两个重要的
观察到发育改变。 首先,尺寸
由于 2 倍的增加,分子显着增加
表达的磷酸化二糖重复单元的数量。
其次,呈现方式也随之减少。
最终暴露的糖。 顺环LPG上的封端糖为
发现介导白蛉中肠的前循环附着,而
元环液化石油气上的这些相同的糖未能介导元环
绑定。 而完整的后环 LPG 不会抑制前环
附着、解聚液化石油气以及原环液化石油气受到抑制,
证明配体通常被掩埋。 曝光度和
随后封端糖的掩蔽解释了这一阶段-
前鞭毛体附着于载体和从载体释放的特异性
中肠,这是可传播疾病发展的关键事件
苍蝇中的感染。
在某些情况下,白荠碱载体只能传播
利什曼原虫的某些种类。 大量对比
载体/寄生虫对揭示了物种特异性差异
在每种情况下,矢量能力都与
前鞭毛体附着于白蛉中肠的能力
其可变结果由结构多态性控制
存在于寄生虫表面的脂磷酸聚糖 (LPG) 中。 数据
表明至少一些静脉注射剂载体在以下方面有所不同
它们表达的寄生虫识别位点以及中肠
粘附力是矢量能力的一个非常重要的组成部分
为LPG结构多态性提供进化驱动力。
中肠特定糖表达缺陷的突变体
使用凝集素或结合的抗体选择附着
到液化石油气的功能域。 LPG突变体已获得
它无法与中肠结合或在苍蝇中生存,而我们是
试图通过功能性修复缺陷基因
互补。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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-- - 项目类别:
Grant-in-Aid for Scientific Research (C)