Involvement of p21(racA), phosphoinositide 3-kinase, and vacuolar ATPase in phagocytosis of bacteria and erythrocytes by Entamoeba histolytica: Suggestive evidence for coincidental evolution of amebic invasiveness
Involvement of p21(racA), phosphoinositide 3-kinase, and vacuolar ATPase in phagocytosis of bacteria and erythrocytes by Entamoeba histolytica: Suggestive evidence for coincidental evolution of amebic invasiveness
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DOI：
10.1128/iai.65.10.4243-4249.1997
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发表时间：
1997-10-01
影响因子：
3.1
通讯作者：
Samuelson, J
中科院分区：
文献类型：
--
作者：
Ghosh, SK;Samuelson, J
溶组织内阿米巴的滋养体，这种原生动物寄生虫可引起阿米巴痢疾，吞噬结肠腔中的细菌和宿主组织中的红细胞（RBC）。因为组织侵入是进化的死胡同，所以很可能是巧合地选择了阿米巴致病性，即，用于杀死结肠腔中细菌的相同方法被寄生虫用来破坏宿主细胞并引起疾病。为了支持这一观点，阿米巴凝集素和成孔肽分别参与细菌和宿主上皮细胞的结合和杀伤。在这里，细菌、红细胞和粘蛋白包被的微珠的阿米巴吞噬作用被E. histolytica p21（racA-V12），一种参与肌动蛋白聚合位点选择的ras家族蛋白，其已被突变以消除其GT3活性。p21（racAV 12）转化体也有缺陷的封盖和胞质分裂，而胞饮的荧光葡聚糖不受影响。磷酸肌醇3-激酶的真菌抑制剂渥曼青霉素显著抑制野生型阿米巴对细菌、RBC和粘蛋白包被珠的吞噬作用。与p21（racA-V12）过表达相反，渥曼青霉素消除了葡聚糖的阿米巴胞饮作用，但对加帽没有抑制作用。巴弗洛霉素对阿米巴空泡酸化的抑制也降低了细菌和红细胞的摄取。这些结果表明，阿米巴和巨噬细胞吞噬细菌和RBC的机制之间的相似性，支持巧合选择阿米巴基因编码介导宿主细胞破坏的蛋白质的想法。
Trophozoites of Entamoeba histolytica, the protozoan parasite that causes amebic dysentery, phagocytose bacteria in the colonic lumen and erythrocytes (RBC) in host tissues. Because tissue invasion is an evolutionary dead end, it is likely that amebic pathogenicity is coincidentally selected, i.e., the same methods used to kill bacteria in the colonic lumen are used by parasites to damage host cells and cause disease. In support of this idea, the amebic lectin and pore-forming peptide are involved in binding and killing, respectively, bacteria and host epithelial cells. Here amebic phagocytosis of bacteria, RBC, and mucin-coated beads was disrupted by overexpression of E. histolytica p21(racA-V12), a ras-family protein involved in selection of sites of actin polymerization, which had been mutated to eliminate its GTPase activity. p21(racAV12) transformants were also defective in capping and cytokinesis, while pinocytosis of fluorescent dextrans was not affected. Wortmannin, a fungal inhibitor of phosphoinositide 3-kinase, markedly inhibited phagocytosis of bacteria, RBC, and mucin-coated beads by wild-type amebae. In contrast to p21(racA-V12) overexpression, wortmannin abolished amebic pinocytosis of dextrans but had no inhibitory effects on capping. Inhibition of amebic vacuolar acidification by bafilomycin also decreased bacterial and RBC uptake. These results, which demonstrate similarities between mechanisms of phagocytosis of bacteria and RBC by amebae and macrophages, support the idea of coincidental selection of amebic genes encoding proteins that mediate destruction of host cells.