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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jul 9

PMID 35805890

Authors

Johanna Detzner

Gottfried Pohlentz

Johannes Muthing

Affiliations

Soon will be listed here.

Abstract

Enterohemorrhagic (EHEC) are the human pathogenic subset of Shiga toxin (Stx)-producing (STEC). EHEC are responsible for severe colon infections associated with life-threatening extraintestinal complications such as the hemolytic-uremic syndrome (HUS) and neurological disturbances. Endothelial cells in various human organs are renowned targets of Stx, whereas the role of epithelial cells of colon and kidneys in the infection process has been and is still a matter of debate. This review shortly addresses the clinical impact of EHEC infections, novel aspects of vesicular package of Stx in the intestine and the blood stream as well as Stx-mediated extraintestinal complications and therapeutic options. Here follows a compilation of the Stx-binding glycosphingolipids (GSLs), globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) and their various lipoforms present in primary human kidney and colon epithelial cells and their distribution in lipid raft-analog membrane preparations. The last issues are the high and extremely low susceptibility of primary renal and colonic epithelial cells, respectively, suggesting a large resilience of the intestinal epithelium against the human-pathogenic Stx1a- and Stx2a-subtypes due to the low content of the high-affinity Stx-receptor Gb3Cer in colon epithelial cells. The review closes with a brief outlook on future challenges of Stx research.

Citing Articles

SARS-CoV-2 enhances complement-mediated endothelial injury via the suppression of membrane complement regulatory proteins.

Wu J, Xu S, Li Z, Cong B, Yang Z, Yang Z Emerg Microbes Infect. 2025; 14(1):2467781.

PMID: 39945674 PMC: 11873982. DOI: 10.1080/22221751.2025.2467781.

Genomic island-encoded regulatory proteins in enterohemorrhagic O157:H7.

Wang F, Sun H, Kang C, Yan J, Chen J, Feng X Virulence. 2024; 15(1):2313407.

PMID: 38357901 PMC: 10877973. DOI: 10.1080/21505594.2024.2313407.

Loop mediated isothermal amplification as a molecular diagnostic assay: Application and evaluation for detection of Enterohaemorrhagic (O157:H7).

Yinur D, Moges B, Hassen A, Tessema T Pract Lab Med. 2023; 37:e00333.

PMID: 37693632 PMC: 10492192. DOI: 10.1016/j.plabm.2023.e00333.

Shiga Toxin (Stx) Type 1a and Stx2a Translocate through a Three-Layer Intestinal Model.

Bova R, Lamont A, Picou T, Ho V, Gilchrist K, Melton-Celsa A Toxins (Basel). 2023; 15(3).

PMID: 36977098 PMC: 10054274. DOI: 10.3390/toxins15030207.

Scientific Discoveries Supporting Theories in Science: From Thinking to Practice.

Fais S Int J Mol Sci. 2022; 23(23).

PMID: 36499354 PMC: 9739909. DOI: 10.3390/ijms232315025.

References

Moxley R, Acuff G . Peri- and Postharvest Factors in the Control of Shiga Toxin-Producing Escherichia coli in Beef. Microbiol Spectr. 2015; 2(6). DOI: 10.1128/microbiolspec.EHEC-0017-2013. View

Merrill Jr A . Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem Rev. 2011; 111(10):6387-422. PMC: 3191729. DOI: 10.1021/cr2002917. View

Frankel G, Phillips A . Attaching effacing Escherichia coli and paradigms of Tir-triggered actin polymerization: getting off the pedestal. Cell Microbiol. 2007; 10(3):549-56. DOI: 10.1111/j.1462-5822.2007.01103.x. View

Bergan J, Lingelem A, Simm R, Skotland T, Sandvig K . Shiga toxins. Toxicon. 2012; 60(6):1085-107. DOI: 10.1016/j.toxicon.2012.07.016. View

Barenholz Y . Sphingomyelin and cholesterol: from membrane biophysics and rafts to potential medical applications. Subcell Biochem. 2004; 37:167-215. DOI: 10.1007/978-1-4757-5806-1_5. View

Bock K, Karlsson K, Stromberg N, Teneberg S . Interaction of viruses, bacteria and bacterial toxins with host cell surface glycolipids. Aspects on receptor identification and dissection of binding epitopes. Adv Exp Med Biol. 1988; 228:153-86. DOI: 10.1007/978-1-4613-1663-3_7. View

Fuller C, Pellino C, Flagler M, Strasser J, Weiss A . Shiga toxin subtypes display dramatic differences in potency. Infect Immun. 2011; 79(3):1329-37. PMC: 3067513. DOI: 10.1128/IAI.01182-10. View

Kanda V, Kitov P, Bundle D, McDermott M . Surface plasmon resonance imaging measurements of the inhibition of Shiga-like toxin by synthetic multivalent inhibitors. Anal Chem. 2005; 77(23):7497-504. DOI: 10.1021/ac050423p. View

Schmidt H, Benz R . Detection and characterization of EHEC-hemolysin. Methods Mol Med. 2002; 73:151-63. DOI: 10.1385/1-59259-316-x:151. View

10.

Schmidt M . LEEways: tales of EPEC, ATEC and EHEC. Cell Microbiol. 2010; 12(11):1544-52. DOI: 10.1111/j.1462-5822.2010.01518.x. View

11.

Varrone E, Carnicelli D, Brigotti M . Extracellular Vesicles and Renal Endothelial Cells: A Fatal Attraction in Hemolytic Uremic Syndrome. Am J Pathol. 2021; 191(5):795-804. DOI: 10.1016/j.ajpath.2021.02.011. View

12.

Quinn P . A lipid matrix model of membrane raft structure. Prog Lipid Res. 2010; 49(4):390-406. DOI: 10.1016/j.plipres.2010.05.002. View

13.

Brigotti M, Tazzari P, Ravanelli E, Carnicelli D, Barbieri S, Rocchi L . Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration. J Leukoc Biol. 2010; 88(1):201-10. DOI: 10.1189/jlb.0709475. View

14.

Simons K, Gerl M . Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol. 2010; 11(10):688-99. DOI: 10.1038/nrm2977. View

15.

Rog T, Vattulainen I . Cholesterol, sphingolipids, and glycolipids: what do we know about their role in raft-like membranes?. Chem Phys Lipids. 2014; 184:82-104. DOI: 10.1016/j.chemphyslip.2014.10.004. View

16.

Robert A, Wiels J . Shiga Toxins as Antitumor Tools. Toxins (Basel). 2021; 13(10). PMC: 8538568. DOI: 10.3390/toxins13100690. View

17.

Nicolson G . Update of the 1972 Singer-Nicolson Fluid-Mosaic Model of Membrane Structure. Discoveries (Craiova). 2020; 1(1):e3. PMC: 7159824. DOI: 10.15190/d.2013.3. View

18.

Cox T . Eliglustat tartrate, an orally active glucocerebroside synthase inhibitor for the potential treatment of Gaucher disease and other lysosomal storage diseases. Curr Opin Investig Drugs. 2010; 11(10):1169-81. View

19.

Sharon N . Carbohydrates as future anti-adhesion drugs for infectious diseases. Biochim Biophys Acta. 2006; 1760(4):527-37. DOI: 10.1016/j.bbagen.2005.12.008. View

20.

Page A, Liles W . Enterohemorrhagic Escherichia coli Infections and the Hemolytic-Uremic Syndrome. Med Clin North Am. 2013; 97(4):681-95, xi. DOI: 10.1016/j.mcna.2013.04.001. View