DEVELOPMENTAL BIOLOGY OF LEISHMANIA PROMASTIGOTES

利什曼原虫前鞭毛体的发育生物学

• 批准号: 3803126
• 负责人: D L SACKS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3803126
• 关键词: Leishmania; Leishmania donovani; Psychodidae; biological polymorphism; communicable disease control; glycolipids; host organism interaction; human subject; human tissue; intracellular parasitism; leishmaniasis; life cycle; microorganism growth; protozoal antigen; surface antigens

During growth within the sand fly and within axenic culture, Leishmania promastigotes undergo differentiation from a dividing noninfective stage to a resting infective or metacyclic stage which is uniquely adapted for life in the vertebrate. For some species of Leishmania (L. donovani and L. major) this development is accompanied by a substantial modification of the surface lipophosphoglycan (LPG) which is the major surface glycoconjugate of these cells. The LPG is densely organized into a glycocalix which effectively masks other surface antigens and which is not expressed on intracellular amastigotes. The complete structures of log phase and metacyclic LPGs of both species have now been determined. The developmental modifications include an elongation of the molecule due to a 2-3 fold increase in the number of phosphorylated oligosaccharated units expressed, and a change in the composition of some of these units. In each case the structural polymorphism is expressed as a loss of terminal galactose residues on the LPG. The effect of this developmental change on the binding of promastigotes to midgut epithelial cells was investigated. An average of 8400 log phase promastigotes bound per midgut, while metacyclic binding was negligible. The binding of log promastigotes was completely inhibited by log phase LPG, but not by metacyclic LPG. The specific oligosaccharide units which mediate the binding is now being studied. In related studies, it was found that the presence of anti-LPG antibodies within an infective bloodmeal inhibited the development of transmissible infections within the sand fly midgut. Thus, immunization of reservoir hosts with LPG may form the basis of a transmission blocking vaccine for leishmaniasis.

在沙蝇和无菌培养物中生长期间，利什曼原虫 前鞭毛体从分裂的非感染阶段分化为 一个独特地适应生命的静止感染或后循环阶段 在脊椎动物中。 对于利什曼原虫的某些种类（L. donovani 和 L. donovani） 主要）这一发展伴随着对 表面脂磷酸聚糖（LPG）是主要的表面糖复合物 这些细胞。 LPG 密集地组织成糖萼， 有效掩盖其他表面抗原，而这些抗原不表达于 细胞内无鞭毛体。 对数相的完整结构 这两个物种的变环液化石油气现已确定。 这 发育修饰包括由于以下原因导致的分子伸长 磷酸化寡糖单位数量增加 2-3 倍 表达，以及其中一些单位的组成的变化。 在每个 在这种情况下，结构多态性表示为末端丢失 LPG 上的半乳糖残留物。 这种发展变化的影响 研究了前鞭毛体与中肠上皮细胞的结合。 每个中肠平均有 8400 个对数期前鞭毛体，而 元环结合可以忽略不计。 对数前鞭毛体的结合是 对数相 LPG 完全抑制，但不被变环 LPG 抑制。 这 目前正在研究介导结合的特定寡糖单元 研究过。 相关研究发现，抗LPG的存在 感染性血粉中的抗体抑制了 白蛉中肠内的传染性感染。 因此，免疫 含有液化石油气的储层主机可能构成传输阻塞的基础 利什曼病疫苗。