Listeriolysin O-dependent host surfaceome remodeling modulates Listeria monocytogenes invasion
Listeriolysin O-dependent host surfaceome remodeling modulates Listeria monocytogenes invasion
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DOI：
10.1093/femspd/fty082
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发表时间：
2018-11-01
影响因子：
3.3
通讯作者：
Pizarro-Cerda, Javier
中科院分区：
文献类型：
--
作者：
Kuehbacher, Andreas;Novy, Karel;Pizarro-Cerda, Javier
单核细胞增多性李斯特菌是一种致病性细菌，其通过激活宿主信号级联来侵入上皮细胞，这促进了吞噬体内的细菌吞噬。细菌吞噬体逃逸所需的成孔毒素嗜酸乳杆菌溶血素O（LLO）也与细胞外细菌分泌的几种信号通路的激活有关，包括Ca 2+内流和促进L.单核细胞增多症定量宿主表面组分析揭示了LLO处理后一组确定的细胞表面糖蛋白的显著定量重塑，包括先前鉴定为在L.单核细胞增多症感染过程。我们的数据进一步表明，溶酶体相关的膜蛋白LAMP-1和LAMP-2易位到细胞表面和这些LLO诱导的Ca 2+通量需要触发表面重新定位的LAMP-1。最后，我们确定晚期内体/溶酶体作为LLO处理后LAMP-1的主要供体区室，并通过干扰它们的功能，我们认为这些细胞器参与了L。单核细胞增多症侵袭。
Listeria monocytogenes is a pathogenic bacterium that invades epithelial cells by activating host signaling cascades, which promote bacterial engulfment within a phagosome. The pore-forming toxin listeriolysin O (LLO), which is required for bacteria phagosomal escape, has also been associated with the activation of several signaling pathways when secreted by extracellular bacteria, including Ca2+ influx and promotion of L. monocytogenes entry. Quantitative host surfaceome analysis revealed significant quantitative remodeling of a defined set of cell surface glycoproteins upon LLO treatment, including a subset previously identified to play a role in the L. monocytogenes infection process. Our data further shows that the lysosomal-associated membrane proteins LAMP-1 and LAMP-2 are translocated to the cellular surface and those LLO-induced Ca2+ fluxes are required to trigger the surface relocalization of LAMP-1. Finally, we identify late endosomes/lysosomes as the major donor compartments of LAMP-1 upon LLO treatment and by perturbing their function, we suggest that these organelles participate in L. monocytogenes invasion.