Cited by 242Escherichia coli research studiesBacterial Genetics and BiotechnologyLipid Membrane Structure and Behavior

Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction

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Lafont, Frank, Van Nhieu, Guy Tran, Hanada, Kentaro, Sansonetti, Philippe, van der Goot, F.Gisou·2002·The EMBO Journal

Abstract

Shigellosis is an acute inflammatory bowel disease caused by the enteroinvasive bacterium SHIGELLA: Upon host cell-Shigella interaction, major host cell signalling responses are activated. Deciphering the initial molecular events is crucial to understanding the infectious process. We identified a molecular complex involving proteins of both the host, CD44 the hyaluronan receptor, and Shigella, the invasin IpaB, which partitions during infection within specialized membrane microdomains enriched in cholesterol and sphingolipids, called rafts. We also document accumulation of cholesterol and raft-associated proteins at Shigella entry foci. Moreover, we report that Shigella entry is impaired after cholesterol depletion using methyl-beta-cyclodextrin. Finally, we find that Shigella is less invasive in sphingosid-based lipid-deficient cell lines, demonstrating the involvement of sphingolipids. Our results show that rafts are implicated in Shigella binding and entry, suggesting that raft-associated molecular machineries are engaged in mediating the cell signalling response required for the invasion process.

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Authors
Lafont, F., Van Nhieu, G. T., Hanada, K., Sansonetti, P., & van der Goot, F. G.
Affiliations
  • University of Geneva (CH)
  • National Institute of Infectious Diseases (JP)
  • Inserm (FR)
Corresponding author
Lafont, Frank
Venue
The EMBO Journal
Published
2002-09-02
Volume
21
Issue
17
Pages
4449-4457
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W1969120551
Cited by
242
References
50
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 11 · 2021: 4 · 2020: 5 · 2019: 12 · 2018: 8 · 2017: 11 · 2016: 14 · 2015: 11 · 2014: 11 · 2013: 11 · 2012: 10
FWCI
9.81
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
Shigella, shigellosis, CD44, IpaB, cholesterol, sphingolipids, lipid rafts, bacterial invasion, host-pathogen interaction, hyaluronan receptor, methyl-β-cyclodextrin, sphingosine
MeSH terms
Animals, Bacterial Adhesion, Bacterial Proteins, Cholesterol, Cricetulus, Cyclodextrins, Cricetinae, HeLa Cells, Humans, Membrane Lipids, Shigella flexneri, Sphingolipids, CHO Cells, Protein Structure, Tertiary, Hyaluronan Receptors, Membrane Microdomains, Protein Interaction Mapping, Macromolecular Substances, beta-Cyclodextrins

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