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首页> 外文期刊>International Journal for Parasitology >Oxidative stress resistance genes contribute to the pathogenic potential of the anaerobic protozoan parasite, Entamoeba histolytica
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Oxidative stress resistance genes contribute to the pathogenic potential of the anaerobic protozoan parasite, Entamoeba histolytica

机译：氧化应激抗性基因有助于厌氧原生动物寄生虫（Entamoeba histolytica）的致病潜力

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摘要

The protozoan parasite, Entamoeba histolytica, invades the host colon causing significant tissue destruction and inflammation. Upon host infection, the parasite is confronted with reactive oxygen and nitrogen species (ROS/RNS) that cause large-scale changes in gene expression profiles, which likely support the parasite's adaptation to the host environment. We have previously identified oxidative and nitrosative stress responsive genes using whole-genome expression profiling. Functional studies on two such genes are now reported and demonstrate that they have roles in parasite virulence. EHI_056680 encodes a small hypothetical protein named E. histolytica stress-induced adhesion factor (EhSIAF); EHI_188210 encodes a putative phospholipid transporting P-type ATPase/flippase (EhPTPA). Over-expression of each protein in E. histolytica trophozoites enhanced parasite survival in response to oxidative stress. Exposure to oxidative and nitrosative stress did not affect the localization of EhSIAF or EhPTPA but markedly increased EhPTPA protein levels. Interestingly, over-expression of each gene resulted in parasites with increased adherence to healthy mammalian cells, but increased adherence to apoptotic cells was noted only in EhSIAF over-expressing parasites. However, despite having increased adherence to both healthy and apoptotic host cells, EhSIAF-over-expressing parasites were reduced in their ability to destroy mammalian cell monolayers, raising the intriguing possibility that EhSIAF over-expression caused signaling defects or resulted in a dominant negative phenotype. Over-expression of EhSIAF and EhPTPA also resulted in decreased motility in a transwell motility assay. Thus, we have confirmed that two genes that are upregulated by ROS confer increased resistance to oxidative stress and have identified an unexpected role of EhSIAF and EhPTPA in host cell adherence and a role of EhSIAF in parasite virulence. Our data imply that stress response genes may play multi-factorial roles in amoebic pathogenesis.
机译：原生动物的寄生虫，组织型变形杆菌，侵入宿主结肠，引起明显的组织破坏和炎症。宿主感染后，该寄生虫会遇到活性氧和氮物质（ROS / RNS），这会导致基因表达谱发生大规模变化，这很可能会支持该寄生虫适应宿主环境。我们以前已经使用全基因组表达谱鉴定了氧化和亚硝化应激反应基因。现在报道了对两个这样的基因的功能研究，并证明它们在寄生虫毒力中起作用。 EHI_056680编码一个小的假设蛋白，称为溶血性大肠杆菌（E. histolytica）应激诱导的粘附因子（EhSIAF）; EHI_188210编码假定的磷脂转运P型ATPase / flippase（EhPTPA）。溶组织大肠杆菌营养体中每种蛋白质的过表达增强了对氧化应激的寄生虫存活。暴露于氧化和亚硝化胁迫下不会影响EhSIAF或EhPTPA的定位，但会显着增加EhPTPA蛋白水平。有趣的是，每个基因的过度表达导致寄生虫对健康哺乳动物细胞的粘附增加，但仅在过表达EhSIAF的寄生虫中才发现对凋亡细胞的粘附增加。然而，尽管增加了对健康和凋亡宿主细胞的依从性，但过表达EhSIAF的寄生虫破坏哺乳动物单层细胞的能力却降低了，这增加了EhSIAF过表达引起信号缺陷或导致显性负表型的可能性。 。 EhSIAF和EhPTPA的过表达在Transwell运动分析中也导致运动降低。因此，我们已经证实了由ROS上调的两个基因赋予了对氧化应激的抗性增强，并确定了EhSIAF和EhPTPA在宿主细胞粘附中的意外作用以及EhSIAF在寄生虫毒力中的作用。我们的数据表明，应激反应基因可能在阿米巴病发病机理中发挥多种作用。

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