Document Detail


Human intestinal tissue and cultured colonic cells contain globotriaosylceramide synthase mRNA and the alternate Shiga toxin receptor globotetraosylceramide.
MedLine Citation:
PMID:  20732996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Escherichia coli O157:H7 and other Shiga toxin (Stx)-producing E. coli (STEC) bacteria are not enteroinvasive but can cause hemorrhagic colitis. In some STEC-infected individuals, a life-threatening sequela of infection called the hemolytic uremic syndrome may develop that can lead to kidney failure. This syndrome is linked to the production of Stx by the infecting organism. For Stx to reach the kidney, the toxin must first penetrate the colonic epithelial barrier. However, the Stx receptor, globotriaosylceramide (Gb3), has been thought to be absent from human intestinal epithelial cells. Thus, the mechanisms by which the toxin associates with and traverses through the intestine en route to the kidneys have been puzzling aspects of STEC pathogenesis. In this study, we initially determined that both types of Stx made by STEC, Stx1 and Stx2, do in fact bind to colonic epithelia in fresh tissue sections and to a colonic epithelial cell line (HCT-8). We also discovered that globotetraosylceramide (Gb4), a lower-affinity toxin receptor derived from Gb3, is readily detectable on the surfaces of human colonic tissue sections and HCT-8 cells. Furthermore, we found that Gb3 is present on a fraction of HCT-8 cells, where it presumably functions to bind and internalize Stx1 and Stx2. In addition, we established by quantitative real-time PCR (qRT-PCR) that both fresh colonic epithelial sections and HCT-8 cells express Gb3 synthase mRNA. Taken together, our data suggest that Gb3 may be present in small quantities in human colonic epithelia, where it may compete for Stx binding with the more abundantly expressed glycosphingolipid Gb4.
Authors:
Steven D Zumbrun; Leanne Hanson; James F Sinclair; James Freedy; Angela R Melton-Celsa; Jaime Rodriguez-Canales; Jeffrey C Hanson; Alison D O'Brien
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-23
Journal Detail:
Title:  Infection and immunity     Volume:  78     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-19     Completed Date:  2010-11-12     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4488-99     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Cells, Cultured
Colon* / cytology,  metabolism
Epithelial Cells / metabolism
Escherichia coli
Escherichia coli Infections
Galactosyltransferases / genetics,  metabolism*
Globosides / metabolism*
Humans
Organ Culture Techniques
RNA, Messenger / genetics,  metabolism
Shiga Toxin 1 / metabolism*
Shiga Toxin 2 / metabolism*
Shiga-Toxigenic Escherichia coli / pathogenicity*
Grant Support
ID/Acronym/Agency:
AI20148/AI/NIAID NIH HHS; AI57168/AI/NIAID NIH HHS; R37 AI020148/AI/NIAID NIH HHS; R37 AI020148-26A1/AI/NIAID NIH HHS; R37 AI020148-27/AI/NIAID NIH HHS; R37 AI020148-29/AI/NIAID NIH HHS; U54 AI057168/AI/NIAID NIH HHS; U54 AI057168-065670/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Globosides; 0/RNA, Messenger; 0/Shiga Toxin 1; 0/Shiga Toxin 2; 11034-93-8/globotetraosylceramide; EC 2.4.1.-/Galactosyltransferases; EC 2.4.1.-/UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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