CHARACTERIZATION OF PSEUDOMONAS-AERUGINOSA-INDUCED MDCK CELL INJURY -GLYCOSYLATION-DEFECTIVE HOST-CELLS ARE RESISTANT TO BACTERIAL KILLING

As a model for bacterium-induced epithelial cell injury, we have studi ed the interaction of Pseudomonas aeruginosa with polarized Madin-Darb y canine kidney (MDCK) cells grown on filters. Following an initial pe riod of bacterial adhesion, foci of injured host cells, which consiste d of a central region of cell debris, surrounded by cells that were pe rmeable and apparently necrotic, were formed. Host cell death was quan tified by measuring the increased permeability of the monolayer to the macromolecular tracer [C-14]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 w as independent of elastase or exotoxin A production. In contrast, bact eria with a mutation in the regulatory locus exsA (which are deficient in exoenzyme S production) neither bound to nor caused host cell inju ry, MDCK cells with defects in cell surface glycosylation were resista nt to cell injury, indicating that bacteria may require host cell glyc olipids and/or glycoproteins as points of adhesion to cause subsequent host cell injury.