Ionophore-resistant mutants of Toxoplasma gondii reveal host cell permeabilization as an early event in egress
Ionophore-resistant mutants of Toxoplasma gondii reveal host cell permeabilization as an early event in egress
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DOI：
10.1128/mcb.20.24.9399-9408.2000
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发表时间：
2000-12-01
影响因子：
5.3
通讯作者：
Boothroyd, JC
中科院分区：
文献类型：
--
作者：
Black, MW;Arrizabalaga, G;Boothroyd, JC
弓形虫是顶复门内的专性细胞内病原体。这种原生动物寄生虫的入侵和排出是快速事件，取决于寄生虫的运动性，并且似乎是由细胞内 [Ca2+] 的波动引导的。用钙离子载体 A23187 处理受感染的宿主细胞会导致寄生虫在称为离子载体诱导排出 (IIE) 的过程中快速排出。相反，当细胞外寄生虫暴露于这种离子载体时，它们很快就会失去感染性（称为离子载体诱导死亡[IID]）。从这里描述的几个 Iie(-) 突变体中，鉴定出两个在几个属性上不同的突变体，最显着的是它们对 IID 的抵抗力。 Iie(-) 和 Iid(-) 表型之间的关联得到以下观察结果的支持：选择为 Iid(-) 的突变体中三分之二也是 Iie(-)。三个不同类别的 IIE 和 IID 突变体的表征表明，lie(-) 表型是由于寄生虫依赖性活性的缺陷造成的，该缺陷通常会导致受感染的宿主细胞在流出之前被透化。当受感染的细胞通过温和的皂苷处理人工透化时，Iie-寄生虫经历了快速的排出，证实了该步骤在Iie-突变体中是有缺陷的。提出了一个模型，其中包括宿主：细胞透化作为导致寄生虫流出的信号通路的关键部分。 Iie(-) 突变体在裂解周期的早期阶段也有缺陷，这一事实表明这些正常过程和 IIE 之间存在一些共性。
Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. Invasion and egress by this protozoan parasite are rapid events that are dependent upon parasite motility and appear to be directed by fluctuations in intracellular [Ca2+]. Treatment of infected host cells with the calcium ionophore A23187 causes the parasites to undergo rapid egress in a process termed ionophore-induced egress (IIE). In contrast, when extracellular parasites are exposed to this ionophore, they quickly lose infectivity (termed ionophore-induced death [IID]). From among several Iie(-) mutants described here, two were identified that differ in several attributes, most notably in their resistance to IID. The association between the Iie(-) and Iid(-) phenotypes Is supported by the observation that two-thirds of mutants selected as Iid(-) are also Iie(-). Characterization of three distinct classes of IIE and IID mutants revealed that the lie(-) phenotype is due to a defect in a parasite-dependent activity that normally causes infected host cells to be permeabilized just prior to egress. Iie- parasites underwent rapid egress when infected cells were artificially permeabilized by a mild saponin treatment, confirming that this step is deficient in the Iie- mutants. A model is proposed that includes host: cell permeabilization as a critical part of the signaling pathway leading to parasite egress. The fact that Iie(-) mutants are also defective in early stages of the lytic cycle indicates some commonality between these normal processes and IIE.