Identification of the carbohydrate receptor for Shiga toxin produced by Shigella dysenteriae type 1.

Lindberg, Alf A.; Brown, J E; Strömberg, Nicklas; Westling-Ryd, M; Schultz, J. E.; Karlsson, Karl‐Anders

doi:10.1016/s0021-9258(19)75706-8

Cited by 425 publications

(73 citation statements)

References 44 publications

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“…3). Similarly, total GSL extracts from CHO cells expressing iGb 3 synthase do not react with the B-subunit of Shiga toxin (35), which specifically binds Gb 3 (20). The globoside and Forssman structures produced in CHO transfected with iGb 3 synthase cDNA must, therefore, be synthesized on the iGb 3 glycolipid, Gal␣1,3Gal␤1,4Glc␤1Cer rather than the more common Gb 3 , Gal␣1,4Gal␤1,4Glc␤1Cer (see Fig.…”

Section: Expression Of Igb 3 Synthase In Cho Cells Leads To the Synthesis Of The Isoglobo-series Gsl-facs Analysis Shows Thatmentioning

confidence: 98%

Expression Cloning of a New Member of the ABO Blood Group Glycosyltransferases, iGb3 Synthase, That Directs the Synthesis of Isoglobo-glycosphingolipids

Keusch¹,

Manzella²,

Nyame³

et al. 2000

Journal of Biological Chemistry

108

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The large array of different glycolipids described in mammalian tissues is a reflection, in part, of diverse glycosyltransferase expression. Herein, we describe the cloning of a UDP-galactose: beta-d-galactosyl-1,4-glucosylceramide alpha-1, 3-galactosyltransferase (iGb(3) synthase) from a rat placental cDNA expression library. iGb(3) synthase acts on lactosylceramide, LacCer (Galbeta1,4Glcbeta1Cer) to form iGb(3) (Galalpha1,3Galbeta1, 4Glcbeta1Cer) initiating the synthesis of the isoglobo-series of glycosphingolipids. The isolated cDNA encoded a predicted protein of 339 amino acids, which shows extensive homology (40-50% identity) to members of the ABO gene family that includes: murine alpha1, 3-galactosyltransferase, Forssman (Gb(5)) synthase, and the ABO glycosyltransferases. In contrast to the murine alpha1, 3-galactosyltransferase, iGb(3) synthase preferentially modifies glycolipids over glycoprotein substrates. Reverse transcriptase-polymerase chain reaction revealed a widespread tissue distribution of iGb(3) synthase RNA expression, with high levels observed in spleen, thymus, and skeletal muscle. As an indirect consequence of the expression cloning strategy used, we have been able to identify several potential glycolipid biosynthetic pathways where iGb(3) functions, including the globo- and isoglobo-series of glycolipids.

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Section: Expression Of Igb 3 Synthase In Cho Cells Leads To the Synthesis Of The Isoglobo-series Gsl-facs Analysis Shows Thatmentioning

confidence: 98%

Expression Cloning of a New Member of the ABO Blood Group Glycosyltransferases, iGb3 Synthase, That Directs the Synthesis of Isoglobo-glycosphingolipids

Keusch¹,

Manzella²,

Nyame³

et al. 2000

Journal of Biological Chemistry

108

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“…Vtx2e is primarily associated with oedema disease in pigs (Marques et al,1987) and is rarely a cause of diarrhoeal disease in humans (Pierard et al, 1991;Scheutz and Ethelberg, 2008;Zweifel et al, 2006) or HUS (Thomas et al, 1994). The differences in Vtx specificity may be due to variation in the genes encoding the B subunits which are responsible for binding of the toxin to the eukaryotic cell receptor (Jacewicz et al, 1986;Lindberg et al, 1987). Vtx2 variants associated with human disease bind primarily to the receptor globotriosyl ceramide found in human kidney cells.…”

Section: Typing Of Virulence Factors and Genesmentioning

confidence: 99%

Scientific Opinion on VTEC‐seropathotype and scientific criteria regarding pathogenicity assessment

Publication¹

2013

EFS2

137

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During 2007During -2010 545 confirmed human VTEC infections and 777 haemolytic uraemic syndrome (HUS) cases were reported in the EU; isolates from 85 % of cases were not fully serotyped and therefore could not be classified using the Karmali seropathotype concept. Seropathotype group D covered 5 % of isolates from fully serotyped cases; 14 cases (0.7 %) belonged to seropathotype group E, defined by Karmali et al. (2003) as nonhuman only. Isolates from around 27 % of cases could not be assigned. There were no HUS cases reported for the serotypes in groups D and E but 17 HUS cases could not be assigned. The health outcome was reported for only a fraction of confirmed cases. About 64 % of patients presented with only diarrhoea; VTEC infection resulted in HUS in around 10 % of cases. The new ISO/TS 13136:2012 standard improves the detection of VTEC in food. An alternative concept based on the detection of verocytotoxins alone or genes encoding such verocytotoxins does not provide a sound scientific basis on which to assess risk to the consumer because there is no single or combination of marker(s) that fully define a "pathogenic" VTEC. Strains positive for verocytotoxin 2 gene (vtx2)-and eae (intimin production)-or [aaiC (secreted protein of EAEC) plus aggR (plasmid-encoded regulator)] genes are associated with higher risk of more severe illness than other virulence gene combinations. The 2011 O104:H4 outbreak demonstrated the difficulty of predicting the emergence of "new" pathogenic VTEC types by screening only for the eae gene or by focusing on a restricted panel of serogroups. A molecular approach utilising genes encoding virulence characteristics additional to the presence of vtx genes has been proposed. The approach adopted entailed a summary of the types of pathogenic E. coli which have been associated with cases of human disease, and the putative virulence factors therein; the use of data from the European Surveillance System (TESSy data) as provided by the ECDC (European Centre for Disease Prevention and Control) and data available in the EU Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Food-borne Outbreaks in 2011 for assessing the current situation regarding human infections with VTEC in the EU; a review of methods for the isolation and identification of VTEC, including detection of virulence factors and characterisation and typing of VTEC strains and virulence genes therein; hazard characterisation, including illnesses associated with VTEC and identification of predictive factors for VTEC that may contribute to human disease; evaluation of the seropathotype concept using the Karmali approach, a modification of the Karmali approach based on the health outcome of reported confirmed human VTEC cases in the EU during 2007-2010, and a molecular approach based on the identification of known or putative colonization genes and additional toxins; and finally exposure assessment, including EU monitoring data on occurrence of VTEC in RTE food. © EuropeanThe BIOHAZ Panel concluded ...

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“…As shown in Figure 1 A, ACHN cells were strongly positive for CD24 by flow cytometry, but negative for CD10. ACHN cells were also found to express low levels of Gb3/CD77, the functional receptor for VTs [22][23][24]. Based on the distribution of various molecules in normal renal tissue [21], ACHN cells in culture may correspond to the epithelium of the distal tubule.…”

Section: Cell Surface Phenotype Of Achn Cellsmentioning

confidence: 99%

Verotoxins induce apoptosis in human renal tubular epithelium derived cells

Taguchi¹,

Uchida²,

Kiyokawa³

et al. 1998

Kidney International

105

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Apoptosis mediated by verotoxins (VTs) has been identified in a renal carcinoma cell line, ACHN cells, which are an in vitro model of renal tubular epithelial cells. ACHN cells express the renal tubular marker CD24 as well as globotriaosyl ceramide/CD77, the receptor for VTs. VT binding to the ACHN cell surface was confirmed by positive staining with antibodies to the VTs. Treatment of ACHN cells with VTs induced prompt growth inhibition and cell death, and fragmentation of the genomic DNA in cells, typical of apoptosis, was observed. The expression of apoptotic antigen 7A6 detected by APO2.7 antibody in ACHN cells further supports the occurrence of apoptosis as a result of VT treatment. Cycloheximide enhanced VT-mediated apoptosis of ACHN cells, suggesting a strong correlation between the inhibition of protein synthesis and VT-mediated apoptosis. Moreover, tumor necrosis factor-alpha had a synergistic effect on VT-mediated apoptosis in ACHN cells. Considering the above evidence together with the clinical evidence showing the presence of apoptosis in the renal epithelium of a HUS patient, our results suggest a VT-induced apoptotic mechanism in normal renal tubular epithelium that may contribute to the pathogenesis of hemolytic uremic syndrome.

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Identification of the carbohydrate receptor for Shiga toxin produced by Shigella dysenteriae type 1.

Cited by 425 publications

References 44 publications

Expression Cloning of a New Member of the ABO Blood Group Glycosyltransferases, iGb3 Synthase, That Directs the Synthesis of Isoglobo-glycosphingolipids

Expression Cloning of a New Member of the ABO Blood Group Glycosyltransferases, iGb3 Synthase, That Directs the Synthesis of Isoglobo-glycosphingolipids

Scientific Opinion on VTEC‐seropathotype and scientific criteria regarding pathogenicity assessment

Verotoxins induce apoptosis in human renal tubular epithelium derived cells

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