Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.

Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.
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受体介导的伤寒毒素从伤寒沙门氏菌感染的细胞中出口期间。

DOI:
10.1016/j.chom.2016.10.005
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发表时间:
2016-11-09
影响因子:
30.3
通讯作者:
Galán JE
Galán JE
中科院分区:
医学1区
文献类型:
--
作者:
Chang SJ;Song J;Galán JE

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伤寒毒素是伤寒沙门氏菌的主要毒力因子,是伤寒的致病菌。伤寒毒素分泌到含沙门氏菌液泡(SCV)的腔中,然后包装到囊泡载体中间体中,并通过尚不完全清楚的机制释放到细胞外。输出后,毒素通过与人特异性Neu 5Ac末端聚糖受体相互作用靶向细胞。我们表明,伤寒毒素从SCV到囊泡载体中间体通过其B亚基,Plt B,与特定的管腔唾液酸化聚糖包装受体的相互作用进行分类。缺乏N-糖基化或特定神经节苷脂合成的细胞,或显示Neu 5Gc-末端聚糖而不是Neu 5Ac-末端聚糖的细胞不支持伤寒毒素输出。此外,伤寒毒素包装需要特定的SCV环境,因为毒素由S.运输受损的伤寒突变体不能正确地分选到囊泡中。这些结果揭示了细胞内病原体的外毒素如何参与宿主途径进行包装和释放。
Typhoid toxin is an essential virulence factor of Salmonella Typhi, the cause of typhoid fever. Typhoid toxin is secreted into the lumen of Salmonella-containing vacuole (SCVs), after which it is packaged into vesicle carrier intermediates and released extracellularly through incompletely understood mechanisms. Following export, the toxin targets cells by interacting with human-specific Neu5Ac-terminated glycan receptors. We show that typhoid toxin is sorted from the SCV into vesicle carrier intermediates via interactions of its B subunit, PltB, with specific lumenal sialylated glycan packaging receptors. Cells deficient in N-glycosylation or the synthesis of specific gangliosides, or displaying Neu5Gc-terminated as opposed to Neu5Ac-terminated glycans do not support typhoid toxin export. Additionally, typhoid toxin packaging requires the specific SCV environment as toxin produced by a S. Typhi mutant with impaired trafficking is not properly sorted into vesicles. These results reveal how the exotoxin of an intracellular pathogen engages host pathways for packaging and release.
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