Invasion and intracellular replication of Salmonella Typhimurium in epithelial cells

鼠伤寒沙门氏菌对上皮细胞的侵袭和细胞内复制

基本信息

批准号：
10927782
负责人：
Olivia Steele-Mortimer
金额：
$ 96.58万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a common cause of enterocolitis in humans and cattle but causes a systemic, typhoid-like, disease in susceptible mice. This facultative intracellular pathogen invades non-phagocytic cells, particularly intestinal epithelial cells. We have previously shown that efficient invasion of intestinal epithelial cells is facilitated by smooth swimming mediated by the chemoreceptor, McpC. We are now studying the role of a second chemoreceptor, McpA, that is co-expressed with McpC. Intracellular replication occurs within the SCV and within the cytosol, bacterial growth rates and transcriptional status within these two intracellular niches are quite different. In particular, the T3SS1 is functionally active in the cytosolic bacteria whereas the T3SS2 is functionally active in the vacuolar bacteria. Thus, each of the T3SS systems are functional in the intracellular environment albeit in different niches. Previously we have developed an environmental autolytic strain, that lysis in the cytosol of mammalian cells, to study the role of the cytosolic population. Using bioengineered Salmonella to either report their intracellular localization (fluorescence protein expression) or to lyse in specific intracellular compartments (lytic gene expression) we are studying how Salmonella intersect signaling pathways in infected epithelial cells and how this impacts survival of the infected host cell or bystanders. Oral infection of naturally resistant mice (e.g. 129X1/SvJ) with Salmonella Typhimurium leads to chronic infection with a small percentage of animals shedding high levels of Salmonella in their feces (super shedders). We are using this model to investigate the factors involved in shedding and persistence and the role played by intestinal epithelial cells.

沙门氏菌性血清鼠伤寒（沙门氏菌伤寒沙门氏菌）是人类和牛的小肠结肠炎的常见原因，但在易感小鼠中引起了全身性，伤寒的疾病。这种辅助细胞内病原体入侵了非吞噬细胞，尤其是肠上皮细胞。我们先前已经表明，通过化学感受器MCPC介导的平滑游泳促进了肠上皮细胞的有效侵袭。我们现在正在研究与MCPC共表达的第二种化学感受器MCPA的作用。细胞内复制发生在SCV内和细胞质内，细菌生长速率和这两个细胞内壁ni的转录状态截然不同。特别是，T3SS1在胞质细菌中具有功能活性，而T3SS2在液泡细菌中具有功能活性。因此，尽管在不同的壁ches中，但每个T3SS系统都在细胞内环境中起作用。以前，我们已经开发出一种环境自溶性菌株，即在哺乳动物细胞的胞质溶胶中裂解，以研究胞质群的作用。使用生物工程的沙门氏菌报告其细胞内定位（荧光蛋白表达）或在特定细胞内室中（裂解基因表达）裂解，我们正在研究沙门氏菌在感染上皮细胞中如何相交的信号通路以及这如何影响感染宿主或旁观者的存活率。口服自然抗性小鼠（例如129x1/svj）用沙门氏菌伤寒的小鼠导致慢性感染，一小部分动物在粪便中散发出高水平的沙门氏菌（超级棚）。我们正在使用该模型来研究脱落和持久性涉及的因素以及肠上皮细胞所起的作用。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A second wave of Salmonella T3SS1 activity prolongs the lifespan of infected epithelial cells.

DOI：
10.1371/journal.ppat.1006354
发表时间：
2017-04
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Finn CE;Chong A;Cooper KG;Starr T;Steele-Mortimer O
通讯作者：
Steele-Mortimer O

The bimodal lifestyle of intracellular Salmonella in epithelial cells: replication in the cytosol obscures defects in vacuolar replication.

DOI：
10.1371/journal.pone.0038732
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Malik-Kale P;Winfree S;Steele-Mortimer O
通讯作者：
Steele-Mortimer O

Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane.

DOI：
10.1111/j.1462-5822.2009.01356.x
发表时间：
2009-11
期刊：
Cellular microbiology
影响因子：
3.4
作者：
Knodler LA;Winfree S;Drecktrah D;Ireland R;Steele-Mortimer O
通讯作者：
Steele-Mortimer O

Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium.

DOI：
10.1016/j.chom.2021.04.017
发表时间：
2021-07-14
期刊：
Cell host & microbe
影响因子：
30.3
作者：
Chong A;Cooper KG;Kari L;Nilsson OR;Hillman C;Fleming BA;Wang Q;Nair V;Steele-Mortimer O
通讯作者：
Steele-Mortimer O

Predictable, Tunable Protein Production in Salmonella for Studying Host-Pathogen Interactions.