Imipenem resistance in Pseudomonas aeruginosa resulting from diminished expression of an outer membrane protein

Abstract

The mechanism of Pseudomonas aeruginosa resistance to imipenem in five imipenem-susceptible clinical isolates and in their resistant counterparts was investigated. The frequency for selecting imipenem-resistant variants ranged from 2.7 X 10(-5) to 2.1 X 10(-8) and was comparable to those for other beta-lactams. Cross-resistance between imipenem and other beta-lactam compounds was not observed. In all imipenem-resistant variants, induction of chromosomal beta-lactamase by imipenem was markedly diminished compared with that in the susceptible parent strain. This was not the case for other inducers such as ampicillin or cefoxitin, suggesting an impaired uptake of imipenem as an explanation for resistance. Analysis of the outer membrane proteins revealed a marked decrease of either a 46- or a 45-kilodalton protein. The lipopolysaccharide of the outer membrane in the imipenem-resistant variants was not altered.