Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium.

Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Research Abstract Details 

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Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Abstract Text:

Daniel M Wall,William J Nadeau,Michael A Pazos,Hai Ning Shi,Edouard E Galyov,Beth A McCormick,

In human intestinal disease induced by Salmonella enterica serotype Typhimurium (S. typhimurium) transepithelial migration of polymorphonuclear leukocytes (PMNs) rapidly follows attachment of the bacteria to the epithelial apical membrane. Previously, we have shown that the S. typhimurium effector protein, SipA, plays a pivotal role in signalling epithelial cell responses that lead to the transepithelial migration of PMNs. Thus, the objective of this study was to determine the functional domain of SipA that regulates this signalling event. SipA was divided into two fragments: the SipAb C-terminal fragment(426-684) (259 AA), which binds actin, and the SipAa fragment(2-425) (424 AA), which a role has yet to be described. In both in vitro and in vivo models of S. typhimurium-induced intestinal inflammation the SipAa fragment exhibited a profound ability to induce PMN transmigration, whereas the SipAb actin-binding domain failed to induce PMN transmigration. Subsequent mapping of the SipAa domain identified a 131-amino-acid region (SipAa3(294-424)) responsible for modulating PMN transepithelial migration. Interestingly, neither intracellular translocation nor actin association of SipA was necessary for its ability to induce PMN transepithelial migration. As these results indicate SipA has at least two separate functional domains, we speculate that during infection S. typhimurium requires delivery of SipA to both extracellular and intracellular spaces to maximize pro-inflammatory responses and mechanisms of bacterial invasion.

Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Publishing Authors By Initials

DM Wall,WJ Nadeau,MA Pazos,HN Shi,EE Galyov,BA McCormick,

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Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cellular microbiology

VOLUME: 9

Page Numbers: 2299-313

Journal Abbreviation: Cell. Microbiol.

ISSN: 1462-5814

DAY: 18

MONTH: 05

YEAR: 2007

Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Information

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LANGUAGE: eng

NlmUniqueID: 100883691

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Grant and Affiliation Information for Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium.

AFFILIATION: Mucosal Immunology Laboratory, Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Charlestown, MA 02129, USA.

Country: England

AGENCY: United States NIDDK

GRANT: DK 56754

ACRONYM: DK

MEDLINETA: Cell Microbiol

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