Cabanes Didier, Sousa Sandra, Cebriá Antonio, Lecuit Marc, García-del Portillo Francisco, Cossart Pascale
Unité des Interactions Bactéries Cellules Institut Pasteur, INSERM U604, INRA USC 2020, Paris, France.
EMBO J. 2005 Aug 3;24(15):2827-38. doi: 10.1038/sj.emboj.7600750. Epub 2005 Jul 14.
By comparative genomics, we have identified a gene of the intracellular pathogen Listeria monocytogenes that encodes an LPXTG surface protein absent from nonpathogenic Listeria species. This gene, vip, is positively regulated by PrfA, the transcriptional activator of the major Listeria virulence factors. Vip is anchored to the Listeria cell wall by sortase A and is required for entry into some mammalian cells. Using a ligand overlay approach, we identified a cellular receptor for Vip, the endoplasmic reticulum (ER) resident chaperone Gp96 recently shown to interact with TLRs. The Vip-Gp96 interaction is critical for bacterial entry into some cells. Comparative infection studies using oral and intravenous inoculation of nontransgenic and transgenic mice expressing human E-cadherin demonstrated a role for Vip in Listeria virulence, not only at the intestine level but also in late stages of the infectious process. Vip thus appears as a new virulence factor exploiting Gp96 as a receptor for cell invasion and/or signalling events that may interfere with the host immune response in the course of the infection.
通过比较基因组学，我们鉴定出细胞内病原体单核细胞增生李斯特菌的一个基因，该基因编码一种在非致病性李斯特菌物种中不存在的LPXTG表面蛋白。这个基因vip受主要李斯特菌毒力因子的转录激活因子PrfA正向调控。Vip通过分选酶A锚定在李斯特菌细胞壁上，是进入某些哺乳动物细胞所必需的。利用配体覆盖法，我们鉴定出Vip的一种细胞受体，即内质网（ER）驻留伴侣蛋白Gp96，最近发现它可与Toll样受体（TLR）相互作用。Vip与Gp96的相互作用对于细菌进入某些细胞至关重要。使用口服和静脉注射非转基因和表达人E-钙黏蛋白的转基因小鼠进行的比较感染研究表明，Vip在李斯特菌毒力中发挥作用，不仅在肠道水平，而且在感染过程的后期阶段。因此，Vip似乎是一种新的毒力因子，利用Gp96作为细胞入侵和/或信号事件的受体，这可能在感染过程中干扰宿主免疫反应。
