Romano Julia D, de Beaumont Catherine, Carrasco Jose A, Ehrenman Karen, Bavoil Patrik M, Coppens Isabelle
Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Eukaryot Cell. 2013 Feb;12(2):265-77. doi: 10.1128/EC.00313-12. Epub 2012 Dec 14.
The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to colonize their host cell and salvage nutrients from organelles. In order to gain fundamental knowledge on the pathogenicity of these microorganisms, we have established a cell culture model whereby single fibroblasts are coinfected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in coinfected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our coinfection studies by examining the respective abilities of Chlamydia and Toxoplasma to co-opt the host cytoskeleton and recruit organelles. We demonstrate that the two pathogen-containing vacuoles migrate independently to the host perinuclear region and rearrange the host microtubular network around each vacuole. However, Toxoplasma outcompetes Chlamydia to the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected with Chlamydia, the centrosomes become associated with the chlamydial inclusion, while the Toxoplasma parasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi apparatus and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by both Chlamydia and Toxoplasma depends on the capability of each pathogen to successfully adhere to a finely tuned developmental program that aims to remodel the host cell for the pathogen's benefit. In particular, this investigation emphasizes the essentiality of host organelle interception by intravacuolar pathogens to facilitate access to nutrients.
沙眼衣原体这种原核生物和刚地弓形虫这种原生动物是人类的两种专性细胞内病原体,它们进化出了相似的运作方式来定殖于宿主细胞并从细胞器中获取营养。为了深入了解这些微生物的致病性,我们建立了一种细胞培养模型,使单个成纤维细胞同时被沙眼衣原体和刚地弓形虫感染。我们之前报道过,这两种病原体在共感染的细胞中争夺相同的营养库,并且弓形虫相对于衣原体具有显著的竞争优势。在此,我们通过研究衣原体和弓形虫各自操控宿主细胞骨架以及招募细胞器的能力,扩展了我们的共感染研究。我们证明,两个含有病原体的液泡独立迁移至宿主核周区域,并在每个液泡周围重新排列宿主微管网络。然而,弓形虫在与衣原体竞争获取宿主微管组织中心方面占优,这对细菌不利,随后细菌转变为应激诱导的持续状态。仅在预先感染衣原体的细胞中,中心体与衣原体包涵体相关联,而弓形虫的寄生泡则出现生长缺陷。两种病原体都会使宿主高尔基体碎片化,并招募高尔基体成分以获取鞘脂。这项研究表明,衣原体和弓形虫的有效感染都取决于每种病原体成功遵循一个精细调节的发育程序的能力,该程序旨在为病原体的利益重塑宿主细胞。特别是,这项研究强调了液泡内病原体拦截宿主细胞器以促进获取营养的必要性。