Jarry Todd M, Cheung Ambrose L
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
Infect Immun. 2006 May;74(5):2568-77. doi: 10.1128/IAI.74.5.2568-2577.2006.
Staphylococcus aureus is frequently the initial bacterium isolated from young cystic fibrosis (CF) patients, and yet its role in CF disease progression has not been determined. Recent data from our lab demonstrates that S. aureus can invade and replicate within the CF tracheal epithelial cell line (CFT-1). Here we describe the finding that the fate of internalized S. aureus in CFT-1 cells differs from its complemented counterpart (LCFSN). S. aureus strain RN6390 was able to replicate within the mutant CFT-1 cells after invasion but not in the complemented LCFSN cells. At 1 h postinvasion, S. aureus containing vesicles within both cell lines acquired vacuolar-ATPase, lysosomal markers LAMP 1 and 2, and the lysomotrophic dye LysoTracker to a similar degree. However, at 4 h postinvasion, the percentage of S. aureus within CFT-1 cells associated with these markers decreased significantly compared to LCFSN, where the association approached 100%. Transmission electron microscopic analysis revealed that the majority of bacteria within CFT-1 cells were free in the cytosol at 4 h after invasion, whereas most S. aureus bacteria internalized by LCFSN cells remained within vesicles. These results demonstrate a fundamental difference in the fate of live S. aureus after invasion of CFT-1 versus LCFSN cell lines and may explain the propensity of S. aureus to cause chronic lung infection in CF patients.
金黄色葡萄球菌常常是从患有囊性纤维化(CF)的年轻患者中最初分离出的细菌,然而其在CF疾病进展中的作用尚未确定。我们实验室最近的数据表明,金黄色葡萄球菌能够在CF气管上皮细胞系(CFT - 1)内侵入并复制。在此我们描述这一发现:内化于CFT - 1细胞中的金黄色葡萄球菌的命运与其互补细胞系(LCFSN)中的不同。金黄色葡萄球菌菌株RN6390在侵入后能够在突变的CFT - 1细胞内复制,但在互补的LCFSN细胞中则不能。侵入后1小时,两种细胞系中含有金黄色葡萄球菌的囊泡均以相似程度获得了液泡型ATP酶、溶酶体标记物LAMP 1和2以及溶酶体营养染料溶酶体示踪剂。然而,侵入后4小时,与这些标记物相关的CFT - 1细胞内金黄色葡萄球菌的百分比与LCFSN相比显著下降,在LCFSN中这种关联接近100%。透射电子显微镜分析显示,侵入后4小时,CFT - 1细胞内的大多数细菌在胞质溶胶中是游离的,而LCFSN细胞内化的大多数金黄色葡萄球菌细菌仍留在囊泡内。这些结果表明,活的金黄色葡萄球菌侵入CFT - 1细胞系与LCFSN细胞系后的命运存在根本差异,这可能解释了金黄色葡萄球菌在CF患者中引起慢性肺部感染的倾向。