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

Frank Lafont, Guy Tran Van Nhieu, Kentaro Hanada, Philippe Sansonetti, F.Gisou van der Goot

Author Affiliations

  1. Frank Lafont*,1,
  2. Guy Tran Van Nhieu2,
  3. Kentaro Hanada3,
  4. Philippe Sansonetti2 and
  5. F.Gisou van der Goot1
  1. 1 Department of Genetics and Microbiology, Centre Medical Universitaire, 1 rue Michel Servet, and Department of Biochemistry, 30 quai Ernest Ansermet, CH‐1211, Geneva 4, Switzerland
  2. 2 Unité de Pathogénie Microbienne Moléculaire, INSERM U389, Institut Pasteur, 28 rue de Dr Roux, F‐75724, Paris, Cedex 15, France
  3. 3 Department of Biochemistry and Cell Biology, National Institute of Infectious diseases, 1‐23‐1, Toyama, Shinjuku‐ku, Tokyo, 162‐8640, Japan
  1. *Corresponding author. E-mail: Frank.Lafont{at}medecine.unige.ch
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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‐β‐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.

  • Received May 30, 2002.
  • Revision received July 15, 2002.
  • Accepted July 15, 2002.
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