THE ROLE OF ADEABC, ADEFGH AND ADEIJK EFFLUX PUMPS IN REDUCED SUSCEPTIBILITY TO TIGECYCLINE IN ACINETOBACTER BAUMANNII ISOLATED FROM BURN PATIENTS

Background and Aim:The wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) Acinetobacter baumannii has led to emergence of tigecycline resistant strains in recent years. In this study the relationship between tigecycline resistance and the expression of efflux pumps was investigated.Methods:Clinical A. baumannii isolates were collected from hospitalized burn patients. The minimum inhibitory concentration (MIC) of tigecycline was determined by the broth microdilution method. Expression levels of efflux pump genes (adeB, adeG, and adeJ) were assessed by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). The correlations between tigecycline MICs and gene expression levels were evaluated. In addition, to confirm observational findings an insertional inactivation using a suicide plasmid construct was performed.Results:Overall, 221 A. baumannii strains isolated from burn wound were investigated among which 29% were tigecycline resistant. Overexpression of AdeABC efflux system was observed in clinical tigecycline resistant isolates. A linear relationship between the tigecycline MIC and the adeB expression level, but not the adeG and adeJ, was found. There were significant linear trends in the overexpression of adeB as the tigecycline MIC increased in A. baumannii isolates. Besides, inactivation of the adeB gene in one tigecycline-susceptible isolate decreased tigecycline MIC from 16 to 1 µg/ml.Conclusion:Tigecycline resistance in A. baumannii was strongly associated with the overexpression of AdeABC efflux systems. More studies are needed to elucidate whether there are other regulators that affect the expression of adeB in A. baumannii

کلیدواژه ها:

Acinetobacter baumannii ، Efflux pump ، Tigecycline