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Human Genome-Wide RNAi Screen for Host Factors That Facilitate Salmonella Invasion Reveals a Role for Potassium Secretion in Promoting Internalization

View Article: PubMed Central - PubMed

ABSTRACT

Salmonella enterica can actively invade the gastro-intestinal epithelium. This frequently leads to diarrheal disease, and also gives the pathogen access to phagocytes that can serve as vehicles for dissemination into deeper tissue. The ability to invade host cells is also important in maintaining the carrier state. While much is known about the bacterial factors that promote invasion, relatively little is known about the host factors involved. To gain insight into how Salmonella enterica serovar Typhimurium is able to invade normally non-phagocytic cells, we undertook a global RNAi screen with S. Typhimurium-infected human epithelial cells. In all, we identified 633 genes as contributing to bacterial internalization. These genes fall into a diverse group of functional categories revealing that cytoskeletal regulators are not the only factors that modulate invasion. In fact, potassium ion transport was the most enriched molecular function category in our screen, reinforcing a link between potassium and internalization. In addition to providing new insights into the molecular mechanisms underlying the ability of pathogens to invade host cells, all 633 host factors identified are candidates for new anti-microbial targets for treating Salmonella infections, and may be useful in curtailing infections with other pathogens as well.

No MeSH data available.


Related in: MedlinePlus

An invasion assay was performed with MCF-7 cells that were untreated or treated with dendrotoxin or treated with dendrotoxin plus potassium or just potassium.An invA::cm strain is included as a control. The experiment was performed in duplicate on two independent occasions. Error bars depict the standard error of the mean. *p-value <0.05
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pone.0166916.g005: An invasion assay was performed with MCF-7 cells that were untreated or treated with dendrotoxin or treated with dendrotoxin plus potassium or just potassium.An invA::cm strain is included as a control. The experiment was performed in duplicate on two independent occasions. Error bars depict the standard error of the mean. *p-value <0.05

Mentions: To confirm the role of potassium secretion in promoting the invasion of epithelial cells by S. Typhimurium, we utilized alpha dendrotoxin, a chemical inhibitor of a subset of voltage-gated potassium channels. In this experiment, cells were either untreated or treated with dendrotoxin or treated with dendrotoxin and potassium and infected with bacteria. We observed that dendrotoxin deters the invasion of epithelial cells by S. Typhimurium and that addition of exogenous potassium to the media alleviates the inhibition (Fig 5).


Human Genome-Wide RNAi Screen for Host Factors That Facilitate Salmonella Invasion Reveals a Role for Potassium Secretion in Promoting Internalization
An invasion assay was performed with MCF-7 cells that were untreated or treated with dendrotoxin or treated with dendrotoxin plus potassium or just potassium.An invA::cm strain is included as a control. The experiment was performed in duplicate on two independent occasions. Error bars depict the standard error of the mean. *p-value <0.05
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120809&req=5

pone.0166916.g005: An invasion assay was performed with MCF-7 cells that were untreated or treated with dendrotoxin or treated with dendrotoxin plus potassium or just potassium.An invA::cm strain is included as a control. The experiment was performed in duplicate on two independent occasions. Error bars depict the standard error of the mean. *p-value <0.05
Mentions: To confirm the role of potassium secretion in promoting the invasion of epithelial cells by S. Typhimurium, we utilized alpha dendrotoxin, a chemical inhibitor of a subset of voltage-gated potassium channels. In this experiment, cells were either untreated or treated with dendrotoxin or treated with dendrotoxin and potassium and infected with bacteria. We observed that dendrotoxin deters the invasion of epithelial cells by S. Typhimurium and that addition of exogenous potassium to the media alleviates the inhibition (Fig 5).

View Article: PubMed Central - PubMed

ABSTRACT

Salmonella enterica can actively invade the gastro-intestinal epithelium. This frequently leads to diarrheal disease, and also gives the pathogen access to phagocytes that can serve as vehicles for dissemination into deeper tissue. The ability to invade host cells is also important in maintaining the carrier state. While much is known about the bacterial factors that promote invasion, relatively little is known about the host factors involved. To gain insight into how Salmonella enterica serovar Typhimurium is able to invade normally non-phagocytic cells, we undertook a global RNAi screen with S. Typhimurium-infected human epithelial cells. In all, we identified 633 genes as contributing to bacterial internalization. These genes fall into a diverse group of functional categories revealing that cytoskeletal regulators are not the only factors that modulate invasion. In fact, potassium ion transport was the most enriched molecular function category in our screen, reinforcing a link between potassium and internalization. In addition to providing new insights into the molecular mechanisms underlying the ability of pathogens to invade host cells, all 633 host factors identified are candidates for new anti-microbial targets for treating Salmonella infections, and may be useful in curtailing infections with other pathogens as well.

No MeSH data available.


Related in: MedlinePlus