Role of Adherence in the Pathogenesis of Pseudomonas aeruginosa Lung Infection in Cystic Fibrosis Patients

Abstract

A correlation was demonstrated between the in vitro adherence of P. aeruginosa to upper respiratory tract epithelium and colonization of the respiratory tract by this organism. Patients (20) with cystic fibrosis (CF) and 20 age-matched controls were examined in this study. All CF patients but none of the controls were colonized with P. aeruginosa at the time of study. P. aeruginosa adherence to isolated epithelial cells, as determined by an in vitro assay, was 19.1 .+-. 1.1 bacteria/buccal epithelial cell in the CF patients and 23 .+-. 0.3 bacteria/cell in the controls (P < 0.01). P. aeruginosa strains of the mucoid colony type adhered in significantly lower numbers to buccal epithelial cells than did strains of the rough colony type (1.8 + 0.1 vs. 24.8 .+-. 0.9, P < 0.001). This difference might explain the common observation that the initial Pseudomonas colonization of the respiratory tract of CF patients is due to organisms of the rough colony type. Increased P. aeruginosa adherence in vitro varies directly with the loss of a protease-sensitive glycoprotein, fibronectin, from the cell surface, and increased levels of salivary proteases in CF patients. When examined by a direct radioimmune binding assay, buccal cells from CF patients possessed only 17% of the total cell surface fibronectin present on similar cells obtained from controls. Salivary protease levels, as measured by 125I release from an 125I-labeled insoluble fibrin matrix, were increased about 3-fold in CF patients vs. controls. Thus, colonization of the respiratory tract by P. aeruginosa in CF patients correlates well with buccal cell adherence of this organism; increased adherence is associated with decreased amounts of fibronectin on respiratory epithelial cell surfaces and increased levels of salivary proteases.