PNAS:在宿主体内和宿主之间传播的沙门氏菌

2010-09-29 00:00 · Prima

一项研究说,导致人类肠胃炎和伤寒的沙门氏菌可能利用了宿主肠道的一个细胞更新过程从而在宿主体内和宿主之间传播。科学家长久以来知道沙门氏菌在宿主肠道上皮细胞的细胞膜结合区室生存和繁殖。但是这种细菌从它们的细胞内藏身处逃离从而感染其他细胞和宿主的机制尚不很清楚。Leigh A. Kno

一项研究说,导致人类肠胃炎和伤寒的沙门氏菌可能利用了宿主肠道的一个细胞更新过程从而在宿主体内和宿主之间传播。科学家长久以来知道沙门氏菌在宿主肠道上皮细胞的细胞膜结合区室生存和繁殖。但是这种细菌从它们的细胞内藏身处逃离从而感染其他细胞和宿主的机制尚不很清楚。Leigh A. Knodler及其同事使用共聚焦显微镜观察了在实验室生长的沙门氏菌感染的人类上皮细胞。

除了存在与膜结合的细菌,这组作者还在一些细胞的细胞质中发现了准备好了入侵其他细胞的超复制细胞群。这组作者报告说,这些细胞具有长鞭状的尾,并且表达了所谓的“针状复合物”的基因,它能帮助沙门氏菌入侵宿主细胞。此外,这组作者发现携带这些入侵性细胞的上皮细胞在一个类似于在肠道上皮正常更新中死去的细胞脱落的过程中从小鼠的上皮层被挤入了肠腔。一旦脱落,这些入侵性的细胞就离开这些死去的细胞,在新的细胞中定居。这组作者说,这些发现提示,在宿主肠细胞中的一群入侵性的细菌偷乘者可能帮助沙门氏菌的传播。

生物谷推荐英文摘要:

PNAS doi: 10.1073/pnas.1006098107

Dissemination of invasive Salmonella via bacterial-induced extrusion of mucosal epithelia

Leigh A. Knodlera,1, Bruce A. Vallanceb, Jean Cellia, Seth Winfreea, Bryan Hansenc, Marinieve Monterob, and Olivia Steele-Mortimera

aLaboratory of Intracellular Parasites and

cResearch Technologies Branch, Microscopy Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; and

bDivision of Gastroenterology, Department of Paediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, BC, Canada V6H 3V4

Salmonella enterica is an intracellular bacterial pathogen that resides and proliferates within a membrane-bound vacuole in epithelial cells of the gut and gallbladder. Although essential to disease, how Salmonella escapes from its intracellular niche and spreads to secondary cells within the same host, or to a new host, is not known. Here, we demonstrate that a subpopulation of Salmonella hyperreplicating in the cytosol of epithelial cells serves as a reservoir for dissemination. These bacteria are transcriptionally distinct from intravacuolar Salmonella. They are induced for the invasion-associated type III secretion system and possess flagella; hence, they are primed for invasion. Epithelial cells laden with these cytosolic bacteria are extruded out of the monolayer, releasing invasion-primed and -competent Salmonella into the lumen. This extrusion mechanism is morphologically similar to the process of cell shedding required for turnover of the intestinal epithelium. In contrast to the homeostatic mechanism, however, bacterial-induced extrusion is accompanied by an inflammatory cell death characterized by caspase-1 activation and the apical release of IL-18, an important cytokine regulator of gut inflammation. Although epithelial extrusion is obviously beneficial to Salmonella for completion of its life cycle, it also provides a mechanistic explanation for the mucosal inflammation that is triggered during Salmonella infection of the gastrointestinal and biliary tracts.

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