A comparison of adeB gene expression levels under conditions of induced resistance by different drugs in vitro in Acinetobacter baumannii

The present study was designed to analyze the difference of the adeB gene expression levels under conditions of induced resistance and to verify the significance of the AdeABC efflux pump in the in vitro induction of Acinetobacter baumannii (A. baumannii). Strains were isolated from blood or drainage samples in the First Hospital of China Medical University. The minimum inhibitory concentration (MIC) was determined by a broth microdilution method. In addition, an in vitro induction of drug-resistance tests was confirmed with the three drugs. The expression level of the adeB was determined by quantitative polymerase chain reaction (qPCR), and there were 19, 17 and 25 strains isolated from this test that were susceptible to amikacin, netilmicin and imipenem, respectively. Furthermore, 11, 15 and 8 stably resistant strains generated against amikacin, netilmicin and imipenem, respectively, by in vitro induction. The MIC values of all the imipenem-sensitive and imipenem-resistant strains decreased by no more than 2-fold under carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-containing conditions. The MIC values of 10 amikacin-resistant and 14 netilmicin-resistant strains decreased 4-fold or more under CCCP-containing conditions. Furthermore, qPCR revealed that none of the imipenem-sensitive or the imipenem-resistant strains expressed the adeB gene, but there were 10 amikacin-resistant and 5 netilmicin-resistant strains that expressed the adeB gene. In conclusion, the present study confirmed that in vitro induction of drug-resistance tests in sensitive A. baumannii strains could produce drug-resistance following long-term exposure to low doses of antibacterial drugs. In addition, amikacin and netilmicin are more prone to producing drug-resistance compared to imipenem in vitro. The results of the efflux phenotype indicate the possible application of CCCP in the inhibition of the efflux system in some drugs. The inconsistency between efflux phenotype and qPCR of adeB indicates that other mechanisms may also be included in the induction of drug-resistance that work with the active mechanism in order to increase drug resistance to common clinically-used antimicrobial drugs.