Beatty Wandy L
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA.
J Cell Sci. 2006 Jan 15;119(Pt 2):350-9. doi: 10.1242/jcs.02733.
Chlamydiae are obligate intracellular bacterial pathogens that replicate solely within the confines of a membrane-bound vacuole termed an inclusion. Within this protected organelle, chlamydiae acquire host-cell-derived biosynthetic precursors necessary for intracellular subsistence, yet the mechanisms and pathways responsible for this acquisition remain elusive. The present study identifies an interaction between the chlamydial inclusion and multivesicular bodies, complex organelles pivotal in protein and lipid transport that are positioned along the endosome-lysosome pathway, and intersect the exocytic pathway in various cell types. Resident protein and lipid constituents of multivesicular bodies colocalized with intracellular chlamydiae, with direct delivery of the resident protein CD63 to the chlamydial inclusion. Interruption of trafficking from multivesicular bodies by pharmacological inhibitors and exogenous antibodies subsequently disrupted sphingolipid delivery to the maturing chlamydial inclusion and intracellular bacterial growth. This study identifies a trafficking pathway from CD63-positive multivesicular bodies to the bacterial inclusion, a novel interaction that provides essential lipids necessary for maintenance of a productive intracellular infection.
衣原体是专性细胞内细菌病原体，仅在称为包涵体的膜结合液泡范围内复制。在这个受保护的细胞器内，衣原体获取细胞内存活所需的宿主细胞衍生生物合成前体，然而负责这种获取的机制和途径仍然难以捉摸。本研究确定了衣原体包涵体与多囊泡体之间的相互作用，多囊泡体是蛋白质和脂质运输中的关键复合细胞器，位于内体 - 溶酶体途径上，并在各种细胞类型中与胞吐途径相交。多囊泡体的驻留蛋白和脂质成分与细胞内衣原体共定位，驻留蛋白CD63直接递送至衣原体包涵体。药理抑制剂和外源抗体对多囊泡体运输的干扰随后破坏了鞘脂向成熟衣原体包涵体的递送以及细胞内细菌的生长。本研究确定了一条从CD63阳性多囊泡体到细菌包涵体的运输途径，这是一种新型相互作用，为维持有效的细胞内感染提供了必需的脂质。
