Subinhibitory concentrations of tetracycline inhibit surface expression of the Pseudomonas aeruginosa ferripyochelin binding protein in vivo

Abstract

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.

Sub-Inhibitory Antibiotic Exposure and Virulence in Pseudomonas aeruginosa

“…Several animal studies describe the protective effects of sub-MIC exposure to tetracycline, ciprofloxacin, tobramycin, and ceftazidime against P. aeruginosa for lung infections in rats and to AZM against P. aeruginosa for renal infections in mice and rats [173,186,240]. However, the mechanism by which the antibiotics achieve this protection is not always understood.…”