Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction.
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.
Department of Genetics and Microbiology, Centre Medical Universitaire, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland. Frank.Lafont@medecine.unige.ch
Frank
F
Lafont
Guy
G
Tran Van Nhieu
Kentaro
K
Hanada
Philippe
P
Sansonetti
F Gisou
FG
van der Goot
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D002784:Cholesterol / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D003505:Cyclodextrins / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000502:physiology*; D046911:Macromolecular Substances; D008563:Membrane Lipids / Q000502:physiology*; D021962:Membrane Microdomains / Q000502:physiology*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012763:Shigella flexneri / Q000187:drug effects / Q000472:pathogenicity*; D013107:Sphingolipids / Q000502:physiology; D047392:beta-Cyclodextrins
D001426:Bacterial Proteins; D003505:Cyclodextrins; D018960:Hyaluronan Receptors; D046911:Macromolecular Substances; D008563:Membrane Lipids; D013107:Sphingolipids; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C087447:ipaB protein, Shigella; D002784:Cholesterol