Plasmodium yoelii S4/CelTOS is important for sporozoite gliding motility and cell traversal.
Plasmodium yoelii S4/CelTOS is important for sporozoite gliding motility and cell traversal.
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约氏疟原虫 S4/CelTOS 对于子孢子的滑动运动和细胞穿越很重要。
DOI：
10.1111/cmi.12817
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发表时间：
2018
影响因子：
3.4
通讯作者：
Kappe,S
中科院分区：
文献类型：
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作者：
Steel,RyanWJ;Pei,Ying;Camargo,Nelly;Kaushansky,Alexis;Dankwa,DorenderA;Martinson,Thomas;Nguyen,Thao;Betz,Will;Cardamone,Hayley;Vigdorovich,Vladimir;Dambrauskas,Nicholas;Carbonetti,Sara;Vaughan,AshleyM;Sather,DNoah;Kappe,S
疟原虫动子和子孢子侵入阶段的滑行运动和细胞穿越允许穿透细胞屏障以分别建立蚊子载体和哺乳动物宿主的感染。在红细胞感染性裂殖子中未观察到运动性和遍历性，我们先前已将在子孢子中表达但不在裂殖子中表达的基因（S基因）分类，以鉴定参与这些过程的蛋白质。S4基因已被描述为关键地参与动孢子和子孢子的细胞迁移（Cell Traffic for Ookinetes and Sporozoites，CelTOS），然而敲除寄生虫（s4/celtos）不产生稳健的唾液腺子孢子数量，排除了在宿主感染期间对S4/CelTOS功能的彻底分析。我们在这里表明，卵囊在中肠中发育或存活的失败有助于约氏疟原虫（Py）s4/celtos？啮齿类疟原虫对蚊子的不良感染。我们通过在动合子特异性环子孢子蛋白和血小板反应蛋白相关的匿名蛋白相关蛋白（CTRP）启动子下表达S4/CelTOS来拯救这种表型。（S4/CelTOSCTRP），产生了大量的缺乏S4/CelTOS的唾液腺子孢子，其适合于表型分析。与野生型子孢子相比，PyS 4/CelTOSCTRP子孢子在BALB/c小鼠中显示出降低的感染性，尽管它们似乎比缺乏相关穿越蛋白PLP 1/SPECT 2（Py plp 1/SPECT 2 ′）的子孢子更具感染性。利用体外试验，我们证实了S4/CelTOS在子孢子细胞穿越中的作用，但也揭示了这种蛋白质在子孢子滑行运动中以前未被认识到的作用。
Gliding motility and cell traversal by thePlasmodiumookinete and sporozoite invasive stages allow penetration of cellular barriers to establish infection of the mosquito vector and mammalian host, respectively. Motility and traversal are not observed in red cell infectious merozoites, and we have previously classified genes that are expressed in sporozoites but not merozoites (S genes) in order to identify proteins involved in these processes. The S4 gene has been described as criticaly involved in Cell Traversal for Ookinetes and Sporozoites (CelTOS), yet knockout parasites (s4/celtos¯) do not generate robust salivary gland sporozoite numbers, precluding a thorough analysis of S4/CelTOS function during host infection. We show here that a failure of oocysts to develop or survive in the midgut contributes to the poor mosquito infection byPlasmodiumyoelii(Py)s4/celtos¯rodent malaria parasites. We rescued this phenotype by expressing S4/CelTOS under the ookinete‐specific circumsporozoite protein and thrombospondin‐related anonymous protein‐related protein (CTRP) promoter (S4/CelTOSCTRP), generating robust numbers of salivary gland sporozoites lacking S4/CelTOS that were suitable for phenotypic analysis.PyS4/CelTOSCTRPsporozoites showed reduced infectivity in BALB/c mice when compared to wild‐type sporozoites, although they appeared more infectious than sporozoites deficient in the related traversal protein PLP1/SPECT2 (Py plp1/spect2¯). Usingin vitroassays, we substantiate the role of S4/CelTOS in sporozoite cell traversal, but also uncover a previously unappreciated role for this protein for sporozoite gliding motility.