Shiga toxin-glycosphingolipid interaction: Status quo of research with focus on primary human brain and kidney endothelial cells - PubMed

Affiliations

• PMID: 30224239
• DOI: 10.1016/j.ijmm.2018.09.003

Review

Shiga toxin-glycosphingolipid interaction: Status quo of research with focus on primary human brain and kidney endothelial cells

Nadine Legros et al. Int J Med Microbiol. 2018 Dec.

Abstract

Shiga toxin (Stx)-mediated injury of the kidneys and the brain represent the major extraintestinal complications in humans upon infection by enterohemorrhagic Escherichia coli (EHEC). Damage of renal and cerebral endothelial cells is the key event in the pathogenesis of the life-threatening hemolytic uremic syndrome (HUS). Stxs are AB₅ toxins and the B-pentamers of the two clinically important Stx subtypes Stx1a and Stx2a preferentially bind to the glycosphingolipid globotriaosylceramide (Gb3Cer, Galα4Galβ4Glcβ1Cer) and to less extent to globotetraosylceramide (Gb4Cer, GalNAcβ3Galα4Galβ4Glcβ1), which are expected to reside in lipid rafts in the plasma membrane of the human endothelium. This review summarizes the current knowledge on the Stx glycosphingolipid receptors and their lipid membrane ensemble in primary human brain microvascular endothelial cells (pHBMECs) and primary human renal glomerular endothelial cells (pHRGECs). Increasing knowledge on the precise initial molecular mechanisms by which Stxs interact with cellular targets will help to develop specific therapeutics and/or preventive measures to combat EHEC-caused diseases.

Keywords: EHEC; Glycosphingolipids; Lipid rafts; Primary endothelial cells; Receptors; Shiga toxin.

Similar articles

• Shiga toxin glycosphingolipid receptors and their lipid membrane ensemble in primary human blood-brain barrier endothelial cells.

  Legros N, Dusny S, Humpf HU, Pohlentz G, Karch H, Müthing J. Legros N, et al. Glycobiology. 2017 Jan;27(1):99-109. doi: 10.1093/glycob/cww090. Epub 2016 Aug 24. Glycobiology. 2017. PMID: 27558838

• Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity.

  Detzner J, Krojnewski E, Pohlentz G, Steil D, Humpf HU, Mellmann A, Karch H, Müthing J. Detzner J, et al. Toxins (Basel). 2021 Feb 12;13(2):139. doi: 10.3390/toxins13020139. Toxins (Basel). 2021. PMID: 33673393 Free PMC article.

• Expression of Shiga toxin 2e glycosphingolipid receptors of primary porcine brain endothelial cells and toxin-mediated breakdown of the blood-brain barrier.

  Meisen I, Rosenbrück R, Galla HJ, Hüwel S, Kouzel IU, Mormann M, Karch H, Müthing J. Meisen I, et al. Glycobiology. 2013 Jun;23(6):745-59. doi: 10.1093/glycob/cwt013. Epub 2013 Feb 21. Glycobiology. 2013. PMID: 23431059

• Enterohemorrhagic Escherichia coli and a Fresh View on Shiga Toxin-Binding Glycosphingolipids of Primary Human Kidney and Colon Epithelial Cells and Their Toxin Susceptibility.

  Detzner J, Pohlentz G, Müthing J. Detzner J, et al. Int J Mol Sci. 2022 Jun 21;23(13):6884. doi: 10.3390/ijms23136884. Int J Mol Sci. 2022. PMID: 35805890 Free PMC article. Review.

• Shiga toxins, glycosphingolipid diversity, and endothelial cell injury.

  Müthing J, Schweppe CH, Karch H, Friedrich AW. Müthing J, et al. Thromb Haemost. 2009 Feb;101(2):252-64. Thromb Haemost. 2009. PMID: 19190807 Review.

Cited by

• Roles of Shiga Toxins in Immunopathology.

  Lee MS, Tesh VL. Lee MS, et al. Toxins (Basel). 2019 Apr 9;11(4):212. doi: 10.3390/toxins11040212. Toxins (Basel). 2019. PMID: 30970547 Free PMC article. Review.

• Innovative and Highly Sensitive Detection of Clostridium perfringens Enterotoxin Based on Receptor Interaction and Monoclonal Antibodies.

  Neumann T, Krüger M, Weisemann J, Mahrhold S, Stern D, Dorner MB, Feraudet-Tarisse C, Pöhlmann C, Schulz K, Messelhäußer U, Rimek D, Gessler F, Elßner T, Simon S, Rummel A, Dorner BG. Neumann T, et al. Toxins (Basel). 2021 Apr 8;13(4):266. doi: 10.3390/toxins13040266. Toxins (Basel). 2021. PMID: 33917845 Free PMC article.

• Core and Accessory Genome Comparison of Australian and International Strains of O157 Shiga Toxin-Producing Escherichia coli.

  Pintara A, Jennison A, Rathnayake IU, Mellor G, Huygens F. Pintara A, et al. Front Microbiol. 2020 Sep 4;11:566415. doi: 10.3389/fmicb.2020.566415. eCollection 2020. Front Microbiol. 2020. PMID: 33013798 Free PMC article.

• Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli.

  Mühlen S, Dersch P. Mühlen S, et al. Front Cell Infect Microbiol. 2020 May 6;10:169. doi: 10.3389/fcimb.2020.00169. eCollection 2020. Front Cell Infect Microbiol. 2020. PMID: 32435624 Free PMC article. Review.

• Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome.

  Detzner J, Pohlentz G, Müthing J. Detzner J, et al. Toxins (Basel). 2020 Jun 4;12(6):373. doi: 10.3390/toxins12060373. Toxins (Basel). 2020. PMID: 32512916 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • ClinicalKey
  • Elsevier Science

• Other Literature Sources

  • scite Smart Citations

• Medical

  • MedlinePlus Health Information