Department of Parasitology, Tokai University School of Medicine, Isehara, Japan.
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Biochem Biophys Res Commun. 2024 Nov 19;734:150468. doi: 10.1016/j.bbrc.2024.150468. Epub 2024 Jul 28.
Entamoeba nuttalli is genetically the closest to Entamoeba histolytica, the causative agent of human amebiasis, and its natural host is Macaca species. A unique E. nuttalli specific surface protein (PTORS) containing 42 repeats of octapeptide was identified by comparative genomic analysis of Entamoeba species. We aimed to elucidate the function of this protein. When trophozoites from various E. nuttalli strains were examined by immunofluorescence microscopy and flow cytometry using a PTORS-specific monoclonal antibody, only a limited proportion of trophozoites were stained, indicating that the protein was not commonly expressed in all E. nuttalli trophozoite. The proportion of trophozoites expressing PTORS increased after passage in hamster livers, suggesting that the protein functions in the virulence of trophozoites in the liver tissue. Single-cell analysis revealed that in the cluster including trophozoites with PTORS gene expression, genes of virulence-related proteins were also upregulated. Trophozoites of E. histolytica transfected with PTORS showed enhanced adherence and subsequent phagocytic activity towards human Jurkat cells, independent of the lectin. E. histolytica trophozoites expressing PTORS formed larger liver abscesses in hamsters. These results demonstrate that PTORS is a novel virulence factor in Entamoeba species.
内蜒阿米巴在基因上与溶组织内阿米巴最为接近，后者是人类阿米巴病的病原体，其天然宿主是猕猴属物种。通过对内阿米巴物种的比较基因组分析，鉴定出一种含有 42 个八肽重复的独特内蜒阿米巴表面蛋白（PTORS）。我们旨在阐明该蛋白的功能。当使用针对 PTORS 的单克隆抗体通过免疫荧光显微镜和流式细胞术检查来自各种内蜒阿米巴株的滋养体时，只有有限比例的滋养体被染色，表明该蛋白并非普遍存在于所有内蜒阿米巴滋养体中。在用仓鼠肝脏传代后，表达 PTORS 的滋养体比例增加，表明该蛋白在肝脏组织中滋养体的毒力中起作用。单细胞分析显示，在包括具有 PTORS 基因表达的滋养体的簇中，与毒力相关的蛋白基因也上调。转染了 PTORS 的溶组织内阿米巴滋养体表现出增强的对人 Jurkat 细胞的黏附和随后的吞噬活性，而与凝集素无关。表达 PTORS 的溶组织内阿米巴滋养体在仓鼠中形成更大的肝脓肿。这些结果表明，PTORS 是内阿米巴物种的一种新型毒力因子。
