title: Pseudomonas aeruginosa exploits a PIP3-dependent pathway to transform apical into basolateral membrane.
abstract: Pseudomonas aeruginosa, an important human pathogen, preferentially binds and enters injured cells from the basolateral (BL) surface. We previously demonstrated that activation of phosphatidylinositol 3-kinase (PI3K) and Akt are necessary and sufficient for P. aeruginosa entry from the apical (AP) surface and that AP addition of phosphatidylinositol 3,4,5-trisphosphate (PIP3) is sufficient to convert AP into BL membrane (Kierbel, A., A. Gassama-Diagne, K. Mostov, and J.N. Engel. 2005. Mol. Biol. Cell. 16:2577-2585; Gassama-Diagne, A., W. Yu, M. ter Beest, F. Martin-Belmonte, A. Kierbel, J. Engel, and K. Mostov. 2006. Nat. Cell Biol. 8:963-970). We now show that P. aeruginosa subverts this pathway to gain entry from the AP surface. In polarized monolayers, P. aeruginosa binds near cell-cell junctions without compromising them where it activates and recruits PI3K to the AP surface. Membrane protrusions enriched for PIP3 and actin accumulate at the AP surface at the site of bacterial binding. These protrusions lack AP membrane markers and are comprised of BL membrane constituents, which are trafficked there by transcytosis. The end result is that this bacterium transforms AP into BL membrane, creating a local microenvironment that facilitates its colonization and entry into the mucosal barrier.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Arlinet
authors.initials: A
authors.lastname: Kierbel
authors.forename: Ama
authors.initials: A
authors.lastname: Gassama-Diagne
authors.forename: Claudia
authors.initials: C
authors.lastname: Rocha
authors.forename: Lilliana
authors.initials: L
authors.lastname: Radoshevich
authors.forename: Joan
authors.initials: J
authors.lastname: Olson
authors.forename: Keith
authors.initials: K
authors.lastname: Mostov
authors.forename: Joanne
authors.initials: J
authors.lastname: Engel
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000382:microbiology*; D004285:Dogs; D007365:Intercellular Junctions / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*
chemical_list: D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate