Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction
Open accessAbstract
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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Bacterial Adhesion and Entry into Host Cells
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“IpaB interacts with the hyaluronic receptor CD44 and mobilizes this host protein in cholesterol-rich lipid rafts, allowing the potential recruitment of other signaling molecules at the site of bacterial entry (Lafont et al., 2002).”
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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
- PMC
- PMC126195
- 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
- green
- europepmc.org
- 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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