The Salmonella SPI2 Effector SseI Mediates Long-Term Systemic Infection by Modulating Host Cell Migration

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The Salmonella SPI2 Effector SseI Mediates Long-Term Systemic Infection by Modulating Host Cell Migration

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dc.contributor.author McLaughlin, Laura M.
dc.contributor.author Govoni, Gregory R.
dc.contributor.author Gerke, Christiane
dc.contributor.author Gopinath, Smita
dc.contributor.author Peng, Kaitian
dc.contributor.author Laidlaw, Grace
dc.contributor.author Chien, Yueh-Hsiu
dc.contributor.author Li, Zhigang
dc.contributor.author Monack, Denise
dc.contributor.author Jeong, Ha-Won
dc.contributor.author Brown, Matthew D.
dc.contributor.author Sacks, David Barry
dc.date.accessioned 2012-01-14T22:07:46Z
dc.date.issued 2009
dc.identifier.citation McLaughlin, Laura M., Gregory R. Govoni, Christiane Gerke, Smita Gopinath, Kaitian Peng, Grace Laidlaw, Yueh-Hsiu Chien, et al. 2009. The SPI2 Effector SseI Mediates Long-Term Systemic Infection by Modulating Host Cell Migration. PLoS Pathogens 5(11): e1000671. en_US
dc.identifier.issn 1553-7366 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:7628366
dc.description.abstract Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically for long periods of time despite the presence of a robust immune response. Chronically infected hosts are asymptomatic and transmit disease to naïve hosts via fecal shedding of bacteria, thereby serving as a critical reservoir for disease. We show that the bacterial effector protein SseI (also called SrfH), which is translocated into host cells by the Salmonella Pathogenicity Island 2 (SPI2) type III secretion system (T3SS), is required for Salmonella typhimurium to maintain a long-term chronic systemic infection in mice. SseI inhibits normal cell migration of primary macrophages and dendritic cells (DC) in vitro, and such inhibition requires the host factor IQ motif containing GTPase activating protein 1 (IQGAP1), an important regulator of cell migration. SseI binds directly to IQGAP1 and co-localizes with this factor at the cell periphery. The C-terminal domain of SseI is similar to PMT/ToxA, a bacterial toxin that contains a cysteine residue (C1165) that is critical for activity. Mutation of the corresponding residue in SseI (C178A) eliminates SseI function in vitro and in vivo, but not binding to IQGAP1. In addition, infection with wild-type (WT) S. typhimurium suppressed DC migration to the spleen in vivo in an SseI-dependent manner. Correspondingly, examination of spleens from mice infected with WT S. typhimurium revealed fewer DC and CD4+ T lymphocytes compared to mice infected with ΔsseI S. typhimurium. Taken together, our results demonstrate that SseI inhibits normal host cell migration, which ultimately counteracts the ability of the host to clear systemic bacteria. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.ppat.1000671 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777311/pdf/ en_US
dash.license LAA
dc.subject immunology en_US
dc.subject cellular microbiology and pathogenesis en_US
dc.subject infectious diseases en_US
dc.subject bacterial infections en_US
dc.title The Salmonella SPI2 Effector SseI Mediates Long-Term Systemic Infection by Modulating Host Cell Migration en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Pathogens en_US
dash.depositing.author Jeong, Ha-Won
dc.date.available 2012-01-14T22:07:46Z
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Pathology en_US

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