Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium.
Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium.
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DOI：
10.1016/j.chom.2021.04.017
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发表时间：
2021-07-14
影响因子：
30.3
通讯作者：
Steele-Mortimer O
中科院分区：
文献类型：
--
作者：
Chong A;Cooper KG;Kari L;Nilsson OR;Hillman C;Fleming BA;Wang Q;Nair V;Steele-Mortimer O
沙门氏菌感染的特征是持续性和间歇性排泄物，这对粪便-口腔传播至关重要。在肠道中，伤寒沙门氏菌(STM)主动侵入肠上皮细胞(IECS)，并在含有沙门氏菌的空泡(SCV)和细胞胞浆中存活。胞浆STM快速复制，表达侵袭因子，并诱导感染的上皮细胞排入肠腔。在这里，我们设计了在胞浆中自毁的STM(STmCytoKill)，但在SCV中正常复制，以检测胞浆STM在感染中的作用。在感染的小鼠模型中，STmCytoKill的肠道扩张和粪便排出受到损害。我们提出了一个模型，在这个模型中，侵袭性STM的反复侵袭、胞浆复制和从挤出的IECS释放，为排泄物所需的高管腔密度提供了燃料。粪便脱落是沙门氏菌在宿主间传播的关键。使用基因工程选择性地清除肠道细胞中的胞质细菌，Chong等人。结果表明，胞浆内的复制促进了肠道内鼠伤寒沙门氏菌的扩张，这是有效地脱落所必需的。
Persistence and intermittent fecal shedding, hallmarks of Salmonella infections, are critical for fecal-oral transmission. In the intestine, Salmonella enterica serovar Typhimurium (STm) actively invades intestinal epithelial cells (IECs) and survives in the Salmonella-containing vacuole (SCV) and the cell cytosol. Cytosolic STm replicates rapidly, expresses invasion factors, and induces extrusion of infected epithelial cells into the intestinal lumen. Here, we engineered STm that self-destructs in the cytosol (STmCytoKill), but replicates normally in the SCV, to examine the role of cytosolic STm in infection. Intestinal expansion and fecal shedding of STmCytoKill are impaired in mouse models of infection. We propose a model whereby repeated rounds of invasion, cytosolic replication and release of invasive STm from extruded IECs, fuels the high luminal density required for fecal shedding. Fecal shedding is crucial for transmission of Salmonella among hosts. Using genetic engineering to selectively deplete cytosolic bacteria from enterocytes, Chong et al. show that intracytosolic replication feeds the expansion of intestinal S. Typhimurium needed for efficient shedding.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
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Finn CE;Chong A;Cooper KG;Starr T;Steele-Mortimer O
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Steele-Mortimer O
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