The effect of sublethal levels of antibiotics on the pathogenicity of Pseudomonas aeruginosa for tracheal tissue

Abstract

Hamster tracheal organ cultures were used to evaluate the ability of two aminoglycoside and two beta-lactam antibiotics to protect the epithelium from damage due to Pseudomonas aeruginosa infection. Hamster tracheal explants were infected with strains of P. aeruginosa for 4 h and washed to remove nonadherent organisms. The explants were incubated for an additional 18 h in fresh minimal essential medium containing inhibitory or subinhibitory concentrations of antibiotics. The explants were examined by scanning electron microscopy and bacterial elastase and exotoxin A production was detected by ELISA and a western blot assay respectively. Concentrations of aminoglycosides below the MIC for the infecting strain protected the epithelium from damage and inhibited the production of exotoxin and elastase. The beta-lactam antibiotics were not protective and epithelial damage was observed at antibiotic levels equal to or higher than the MIC for that strain. The beta-lactam treated cultures continued to release elastase and exotoxin A at antibiotic concentrations equivalent to or higher than the MIC for that strain. Thus subinhibitory levels of aminoglycoside antibiotics could protect the infected epithelium from damage by inhibiting the release of toxic substances from the invading bacteria. In contrast, bacteria exposed to beta-lactam antibiotics may continue to release extracellular toxins which can damage the tissue.