Center for Research on Intracellular Bacteria (CRIB), Institute of Microbiology, University Hospital Center and University of Lausanne, 1011 Lausanne, Switzerland.
Microbiology (Reading). 2010 Feb;156(Pt 2):340-355. doi: 10.1099/mic.0.034546-0. Epub 2009 Nov 19.
Waddlia chondrophila is an obligate intracellular bacterium considered as a potential agent of abortion in both humans and bovines. This member of the order Chlamydiales multiplies rapidly within human macrophages and induces lysis of the infected cells. To understand how this Chlamydia-like micro-organism invades and proliferates within host cells, we investigated its trafficking within monocyte-derived human macrophages. Vacuoles containing W. chondrophila acquired the early endosomal marker EEA1 during the first 30 min following uptake. However, the live W. chondrophila-containing vacuoles never co-localized with late endosome and lysosome markers. Instead of interacting with the endosomal pathway, W. chondrophila immediately co-localized with mitochondria and, shortly after, with endoplasmic reticulum- (ER-) resident proteins such as calnexin and protein disulfide isomerase. The acquisition of mitochondria and ER markers corresponds to the beginning of bacterial replication. It is noteworthy that mitochondrion recruitment to W. chondrophila inclusions is prevented only by simultaneous treatment with the microtubule and actin cytoskeleton-disrupting agents nocodazole and cytochalasin D. In addition, brefeldin A inhibits the replication of W. chondrophila, supporting a role for COPI-dependent trafficking in the biogenesis of the bacterial replicating vacuole. W. chondrophila probably survives within human macrophages by evading the endocytic pathway and by associating with mitochondria and the ER. The intracellular trafficking of W. chondrophila in human macrophages represents a novel route that differs strongly from that used by other members of the order Chlamydiales.
脆质支原体是一种严格的细胞内细菌，被认为是人类和牛流产的潜在病原体。这种衣原体目成员在人类巨噬细胞内快速繁殖，并诱导受感染细胞溶解。为了了解这种类似衣原体的微生物如何侵入和在宿主细胞内增殖，我们研究了它在单核细胞衍生的人类巨噬细胞内的运输。在摄取后最初 30 分钟内，含有脆质支原体的空泡获得早期内体标记物 EEA1。然而，活的含有脆质支原体的空泡从未与晚期内体和溶酶体标记物共定位。脆质支原体没有与内体途径相互作用，而是立即与线粒体共定位，随后与内质网 (ER) 驻留蛋白如钙连蛋白和蛋白二硫键异构酶共定位。获得线粒体和 ER 标记物对应于细菌复制的开始。值得注意的是，只有同时用微管和肌动蛋白细胞骨架破坏剂诺考达唑和细胞松弛素 D 处理，才能阻止线粒体向脆质支原体包含物的募集。此外，布雷菲德菌素 A 抑制脆质支原体的复制，支持 COPI 依赖性运输在细菌复制空泡生物发生中的作用。脆质支原体可能通过逃避内吞途径并与线粒体和 ER 相关联而在人类巨噬细胞内存活。在人类巨噬细胞中，脆质支原体的细胞内运输代表了一种与其他衣原体目成员使用的途径强烈不同的新途径。
