Two studies were conducted to determine whether Pseudomonas aeruginosa exoenzyme expression was increased during pulmonary exacerbations of cystic fibrosis (CF) and if it was reduced by antibiotic therapy. The first study was retrospective comparing in vitro exoenzyme levels expressed by P. aeruginosa sputum isolates from seriously ill, hospitalized patients with CF to those from P. aeruginosa strains isolated from CF clinic patients who were in relatively better health. Exoenzyme values were significantly greater in P. aeruginosa strains isolated from ill, hospitalized patients than in clinic patients (P = 0.0001). In the prospective study, in vitro exoenzyme levels were measured from sputum P. aeruginosa isolates of 9 hospitalized patients with CF. Exoenzyme values were greatest in nonmucoid strains on admission (P < 0.0025), and P. aeruginosa exoenzyme expression decreased significantly during hospitalization (P < 0.0025). Deterioration in CF lung disease was accompanied by increased P. aeruginosa exoenzyme production, especially by nonmucoid strains. Antibiotic treatment during hospitalization resulted in mean improvement of % predicted forced expiratory volume in 1 sec (FEV1) from 39 to 53% (P = 0.002). Thus, antibiotics may improve pulmonary function in patients with CF by decreasing P. aeruginosa exoenzyme expression.
The effects of subinhibitory concentrations of tetracycline on surface expression of Pseudomonas aeruginosa ferripyochelin binding protein (FBP) and P. aeruginosa virulence in a pulmonary infection model in rats were examined. Rats were inoculated intratracheally with P. aeruginosa strain DG1 embedded in agar beads. One half of the inoculated animals served as untreated controls while the other half received daily injections of 15 mg/kg tetracycline. FBP was shown to be surface exposed in bacteria isolated from control animals using indirect immunofluorescence and immunoelectron microscopy. No FBP was detectable, however, on the surface of bacteria isolated from the lungs of animals treated with tetracycline. The numbers of bacteria recovered from the lungs of infected animals did not differ between control and tetracycline treated groups, although the degree of pathology observed in tetracycline treated animals was significantly lower than in untreated controls (P = 0.002, one way ANOVA). Sub-inhibitory doses of tetracycline reduced proteolytic activity in vitro, but had no effect on the activities of exotoxin A or exoenzyme S. These studies suggest that exposure to subinhibitory concentrations of tetracycline can repress FBP surface expression as well as proteolytic activity in P. aeruginosa leading to a significant decrease in lung injury during infections due to this organism.
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