title: Characterization of Pseudomonas aeruginosa-induced MDCK cell injury: glycosylation-defective host cells are resistant to bacterial killing.
abstract: As a model for bacterium-induced epithelial cell injury, we have studied the interaction of Pseudomonas aeruginosa with polarized Madin-Darby canine kidney (MDCK) cells grown on filters. Following an initial period of bacterial adhesion, foci of injured host cells, which consisted of a central region of cell debris, surrounded by cells that were permeable and apparently necrotic, were formed. Host cell death was quantified by measuring the increased permeability of the monolayer to the macromolecular tracer [14C]inulin. Using this MDCK model system, we have identified bacterial and host cell factors necessary for the host cell damage. The ability of P. aeruginosa to cause MDCK cell damage was independent of elastase or exotoxin A production. In contrast, bacteria with a mutation in the regulatory locus exsA (which are deficient in exoenzyme S production) neither bound to nor caused host cell injury. MDCK cells with defects in cell surface glycosylation were resistant to cell injury, indicating that bacteria may require host cell glycolipids and/or glycoproteins as points of adhesion to cause subsequent host cell injury.
authors.affiliation: Department of Anatomy, University of California, San Francisco 94143.
authors.forename: G
authors.initials: G
authors.lastname: Apodaca
authors.forename: M
authors.initials: M
authors.lastname: Bomsel
authors.forename: R
authors.initials: R
authors.lastname: Lindstedt
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: D
authors.initials: D
authors.lastname: Frank
authors.forename: K E
authors.initials: KE
authors.lastname: Mostov
authors.forename: J
authors.initials: J
authors.lastname: Wiener-Kronish
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D002470:Cell Survival; D003208:Concanavalin A / Q000494:pharmacology; D004285:Dogs; D006001:Glycoconjugates / Q000378:metabolism; D006031:Glycosylation; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology; D008854:Microscopy, Electron; D008954:Models, Biological; D010539:Permeability; D037121:Plant Lectins; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*
chemical_list: D006001:Glycoconjugates; D037102:Lectins; D037121:Plant Lectins; C017707:Ricinus communis agglutinin-1; D003208:Concanavalin A