Biomedical subjects

Frank Lafont

Publications and source records attributed to Frank Lafont.

5 recordsLinked to original sources

PubMed2005

Oiling the key hole.

Many bacteria have been found to interact with specialized domains, rich in cholesterol and sphingolipids, of the host plasma membrane, termed lipid rafts. The mechanisms that underlie this interaction are starting to be unravelled. In this issue, Hayward et al. show that early effector proteins secreted by type III secretion harbouring Gram-negative bacteria are in fact cholesterol-binding proteins. Combined with other recent findings, this work shows that multiple steps leading to infection by these bacteria depend on raft components: activation of secretion, binding, perforation of the host cell membrane and signalling to trigger bacterial engulfment.

Bacteria↗

PubMed2005

Bacterial invasion via lipid rafts.

Accumulating reports document the use by pathogens of cholesterol-enriched lipid microdomains, often called lipid rafts, as cell surface platforms to interact, bind and possibly enter into host cells. The challenge is now to understand what could be the functional role of these domains during pathogen invasion. Are they hijacked as general clustering devices for cellular binding sites and/or do they have other roles? In particular, is their cell signalling capacity activated and used by pathogens? In reverse, could lipid rafts activate bacterial mechanisms required for invasion? These issues will be discussed after an introduction on the current view on lipid rafts.

Animals↗

PubMed2004

Rafts can trigger contact-mediated secretion of bacterial effectors via a lipid-based mechanism.

Infection by the Gram-negative bacterial pathogen Shigella flexneri depends on its ability to invade host cells. Bacterial engulfment requires a functional type III secretion system (TTSS) allowing the translocation into host cells of bacterial effectors that activate cell-signaling cascades. We demonstrated previously that specialized lipid membrane domains enriched in cholesterol and sphingolipids (rafts) are involved during early steps of invasion, namely in binding and host cell entry. In this study, we addressed the issue of contact-mediated secretion by the TTSS. We show that contact-mediated and TTSS-induced hemolysis depend on the presence of cholesterol on the host cell surface. We found that purified detergent resistant membranes were able to activate TTSS. Finally, we found that artificial liposomes, devoid of proteins, were able to activate the TTSS but only when their composition mimicked that of lipid rafts. Altogether, these data indicate that specific lipid packing can trigger contact-mediated secretion by S. flexneri.

Animals↗

PubMed2004

Bacterial subversion of lipid rafts.

Bacteria rely on numerous basic cellular functions of their target cells to reach successful infection. The recent discovery that the plasma membrane contains specialized microdomains, called lipid rafts, with many specific functions but in particular with the ability to concentrate signaling molecules, has therefore attracted the attention of cellular microbiologists. Since then an increasing number of bacteria and their products have been shown to interact with lipid rafts to promote infection or intoxication. Here we review why certain bacteria and/or their products are attracted toward these lipid microdomains.

Animals↗

PubMed2002

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.

Animals↗