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The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi

机译:阶段调节的HASPB和SHERP蛋白对于沙蝇载体Phlebotomus papatasi的原生动物寄生虫利什曼原虫的分化至关重要

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摘要

The stage-regulated HASPB and SHERP proteins of Leishmania major are predominantly expressed in cultured metacyclic parasites that are competent for macrophage uptake and survival. The role of these proteins in parasite development in the sand fly vector has not been explored, however. Here, we confirm that expression of HASPB is detected only in vector metacyclic stages, correlating with the expression of metacyclic-specific lipophosphoglycan and providing the first definitive protein marker for this infective sand fly stage. Similarly, SHERP is expressed in vector metacyclics but is also detected at low levels in the preceding short promastigote stage. Using genetically modified parasites lacking or complemented for the LmcDNA16 locus on chromosome 23 that contains the HASP and SHERP genes, we further show that the presence of this locus is essential for parasite differentiation to the metacyclic stage in Phlebotomus papatasi. While wild-type and complemented parasites transform normally in late-stage infections, generating metacyclic promastigotes and colonizing the sand fly stomodeal valve, null parasites accumulate at the earlier elongated nectomonad stage of development within the abdominal and thoracic midgut of the sand fly. Complementation with HASPB or SHERP alone suggests that HASPB is the dominant effector molecule in this process.
机译:大利什曼原虫的阶段调节HASPB和SHERP蛋白主要在培养的巨环寄生虫中表达,这些寄生虫能够吸收巨噬细胞并存活。但是,尚未研究这些蛋白质在沙蝇载体中寄生虫发育中的作用。在这里,我们证实,HASPB的表达仅在载体的亚循环阶段被检测到,与亚循环特异性脂磷聚糖的表达相关,并为该传染性沙蝇阶段提供了第一个确定的蛋白质标记。类似地,SHERP在载体元环中表达,但在先前的短鞭毛前期阶段也以低水平检测到。使用缺少或补充含有HASP和SHERP基因的23号染色体上LmcDNA16基因座的基因改造的寄生虫,我们进一步表明,该基因座的存在对于将寄生虫分化为番木瓜的中期循环至关重要。尽管野生型和互补性寄生虫在后期感染中通常会发生转化,产生超环前鞭毛体并在沙蝇的足突瓣中定植,但空寄生虫会在沙蝇的腹和胸中肠内的较早的线状单胞菌发育阶段蓄积。单独与HASPB或SHERP互补表示HASPB是此过程中的主要效应分子。

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