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Identification of the Salmonella typhimurium SipA functional domain required for intestinal inflammation
Author(s) -
Wall Daniel M,
McCormick Beth A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a587-b
Subject(s) - effector , biology , inflammation , microbiology and biotechnology , intestinal epithelium , in vivo , salmonella , immunology , epithelium , bacteria , genetics
The pathognomonic feature of salmonellosis, as well as inflammatory bowel disease (IBD), which is correlated with patient symptomatology, is the transepithelial migration of neutrophils (PMN) across intestinal epithelia and into the luminal space to form crypt abscesses. We have shown that this final step of PMN movement across the intestinal epithelium to be directed by the eicosanoid hepoxilin A 3 (HXA 3 ) and is dependent on Salmonella typhimurium type III secreted effector protein SipA. The objective of this study was to determine the functional domain of SipA that regulates this signaling event underlying PMN transepithelial migration, and hence intestinal inflammation. SipA was divided into two fragments; the SipAb C‐terminal fragment (259 AA), which binds actin, and the SipAa fragment (425 AA), which no role has yet to be described. Using both in vitro and in vivo models of intestinal inflammation the SipAa fragment exhibited a profound ability to induce PMN transmigration, but failed to bind actin, whereas the SipAb fragment bound actin but failed to induce PMN transmigration. Truncation analysis of the SipAa fragment revealed that the functional domain is harbored between base pairs 901 and 1275. Interesting, unlike other bacterial effector proteins the SipAa fragment was found to act extracellularly and presumably binds to a surface receptor. Thus, by investigating the events that occur at the S. typhimurium ‐intestinal interface involving the effector SipA, we can begin to define the initial surface interactions, which are thought to trigger the subsequent inflammatory response.