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Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation


During infection, Shigella spp. deliver into the cytoplasm of cells effector proteins that manipulate host cell processes in ways that promote infection and bacterial spread. We have discovered that the Shigella effector protein OspB interacts with the cellular scaffolding protein IQGAP1. OspB induces increased cell proliferation by activating mTORC1 kinase, a master regulator of cellular growth, in a manner that depends on IQGAP1. As IQGAP1 has been shown to interact with mTOR and with the mTORC1 activators ERK1/2, we propose that IQGAP1 serves as a scaffold for OspB activation of mTORC1. The presence of OspB and IQGAP1 lead to restricting the area of spread of S. flexneri in cell monolayers; our data support a model in which the effect of OspB and IQGAP1 on the area of S. flexneri spread is due to effects on cell proliferation locally within infected foci. As infection of cells and tissue by Shigella spp. leads to cell death, increased local cellular proliferation may serve to provide additional protective intracellular niches for the organism within infected tissue.


Vyšlo v časopise: Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005200
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005200

Souhrn

During infection, Shigella spp. deliver into the cytoplasm of cells effector proteins that manipulate host cell processes in ways that promote infection and bacterial spread. We have discovered that the Shigella effector protein OspB interacts with the cellular scaffolding protein IQGAP1. OspB induces increased cell proliferation by activating mTORC1 kinase, a master regulator of cellular growth, in a manner that depends on IQGAP1. As IQGAP1 has been shown to interact with mTOR and with the mTORC1 activators ERK1/2, we propose that IQGAP1 serves as a scaffold for OspB activation of mTORC1. The presence of OspB and IQGAP1 lead to restricting the area of spread of S. flexneri in cell monolayers; our data support a model in which the effect of OspB and IQGAP1 on the area of S. flexneri spread is due to effects on cell proliferation locally within infected foci. As infection of cells and tissue by Shigella spp. leads to cell death, increased local cellular proliferation may serve to provide additional protective intracellular niches for the organism within infected tissue.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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