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首页> 外文期刊>Infection and immunity >Survival of Tropheryma whipplei, the Agent of Whipple's Disease, Requires Phagosome Acidification
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Survival of Tropheryma whipplei, the Agent of Whipple's Disease, Requires Phagosome Acidification

机译：Whipple病病原体whipplei的生存需要将Phagosome酸化

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Tropheryma whipplei was established as the agent of Whipple's disease in 2000, but the mechanisms by which it survives within host cells are still unknown. We show here that T. whipplei survives within HeLa cells by controlling the biogenesis of its phagosome. Indeed, T. whipplei colocalized with lysosome-associated membrane protein 1, a membrane marker of late endosomal and lysosomal compartments, but not with cathepsin D, a lysosomal hydrolase. This defect in phagosome maturation is specific to live organisms, since heat-killed bacilli colocalized with cathepsin D. In addition, T. whipplei survived within HeLa cells by adapting to acidic pH. The vacuoles containing T. whipplei were acidic (pH 4.7 ± 0.3) and acquired vacuolar ATPase, responsible for the acidic pH of late phagosomes. The treatment of HeLa cells with pH-neutralizing reagents, such as ammonium chloride, N-ethylmaleimide, bafilomycin A1, and chloroquine, increased the intravacuolar pH and promoted the killing of T. whipplei. The ability of T. whipplei to survive in an acidic environment and to interfere with phagosome-lysosome fusion is likely critical for its prolonged persistence in host cells during the course of Whipple's disease. Our results suggest that manipulating the intravacuolar pH may provide a new approach for the treatment of Whipple's disease.
机译：2000年， Tropheryma whipplei 被确立为Whipple病的病原体，但其在宿主细胞中存活的机制仍不清楚。我们在这里显示 T。 Whipplei 通过控制其吞噬体的生物发生而在HeLa细胞中存活。确实， T。 whipplei 与溶酶体相关膜蛋白1（一种晚期内体和溶酶体区室的膜标志物）共定位，但不与组织蛋白酶D（一种溶酶体水解酶）共定位。吞噬体成熟的缺陷是活生物体特有的，因为热杀死的细菌与组织蛋白酶D共定位。此外， T。 Whipplei 通过适应酸性pH在HeLa细胞中存活。含有 T的液泡。 Whipplei呈酸性（pH 4.7±0.3）并获得液泡ATPase，这是晚期吞噬体的酸性pH值。用氯化铵， N -乙基马来酰亚胺，bafilomycin A1和氯喹等中和pH的试剂处理HeLa细胞，可提高血管内pH并促进 T的杀伤。 whipplei 。 T的能力。 whipplei 能够在酸性环境中生存并干扰吞噬体-溶酶体融合，这可能是其在Whipple病过程中在宿主细胞中持久存在的关键。我们的研究结果表明，调节血管内pH可能为治疗Whipple病提供一种新方法。

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