Bacterial Penetration of the Mucosal Barrier by Targeting Lipid Rafts

ABSTRACTSeveral traditionally extracellular pathogens not known to possess invasive capacity have been shown to invade various mucosal epithelial cells. The mucosal epithelium performs an important barrier function and is not typically amenable to bacterial invasion. Valuable clues to the underlying basis for bacterial invasion have emerged from recent studies examining the invasion of bladder epithelial cells by uropathogenic Escherichia coli and alveolar epithelial cells by Pseudomonas aeruginosa. In both cases, bacterial invasion is achieved through targeting of molecules specifically found within distinct glycosphingolipid- and cholesterol-enriched microdomains called lipid rafts. The importance of lipid rafts in promoting bacterial invasion was shown as disruptors of lipid rafts blocked cellular invasion by both E. coli and P. aeruginosa. In addition, molecular components of lipid rafts were found to be highly enriched in membranes encasing these intracellular bacteria. Furthermore, caveolin proteins, which serve to stabilize and organize lipid raft components, are necessary for bacterial entry. Taken together, targeting of lipid rafts appears to be an effective but poorly recognized mechanism used by pathogenic bacteria to circumvent the mucosal barriers of the host.