TRANSIENT CARBAPENEM RESISTANCE INDUCED BY SALICYLATE IN PSEUDOMONAS-AERUGINOSA ASSOCIATED WITH SUPPRESSION OF OUTER-MEMBRANE PROTEIN D2 SYNTHESIS

Pseudomonas aeruginosa PA01 showed increased phenotypic resistance to imipenem, panipenem, and biapenem specifically in the presence of sali cylate. The antipseudomonal activity of carbapenems was reduced in pro portion to the concentration of salicylate. This resistance was transi ent and nonheritable. The synthesis of the outer membrane protein D2 ( OprD or OprD2) in P. aeruginosa PA01 was inhibited by 4 to 32 mM salic ylate in the bacterial growth medium, whereas no changes in any other outer membrane proteins were observed. These results indicate that sal icylate suppresses the synthesis of OprD and therefore reduces the ant ipseudomonal activity of carbapenems. Under these conditions, one carb apenem-meropenem-is still active against P. aeruginosa, which indicate s that meropenem can pass through the outer membrane via both the D2 c hannel and another undefined route(s).