Distribution of AdeABC efflux system genes in Acinetobacter baumannii isolated from blood cultures of hospitalized patients and their relationship with carbapenem and aminoglycoside resistance [Kan kültürlerinden İzole edilen Acinetobacter baumannii İzolatlarında AdeABC efluks pompası genlerinin dağılımı ve karbapenem-aminoglikozit direnci ile İlişkisinin araştırılması]

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Galenos Publishing House

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Introduction: The increasing emergence of multidrug-resistant (MDR) Acinetobacter infections has become a significant challenge for physicians and clinical microbiologists owing to the difficulties arising during therapy. The major efflux mechanism associated with MDR in A. baumannii is the chromosomally encoded tripartite efflux pump, AdeABC, which has been reported worldwide. AdeABC belongs to the resistance-nodulation-division efflux pump family and has a three-component structure: AdeB forms the transmembrane component, AdeA forms the inner membrane fusion protein, and AdeC forms the outer membrane protein. AdeABC is chromosomally encoded and is regulated by a two-component system containing a sensor kinase (AdeS) and its associated response regulator (AdeR). Point mutations in these components are associated with the overexpression of AdeABC, thereby leading to multiple drug resistance. The purpose of this study was to investigate the distribution of the AdeABC efflux pump genes and their relationship with carbapenem and multiple drug resistance in A. baumannii strains isolated from the blood cultures of hospitalized patients. Materials and Methods: A total of 97 A. baumannii strains that were isolated from the blood cultures of hospitalized patients in different departments, were included in the study. The Phoenix Automated System was used to identify and determine antibiotic susceptibility patterns. The susceptibility of the study strains to carbapenems, ciprofloxacin, trimethoprim-sulfamethoxazole, amikacin, gentamicin, and netilmicin were determined according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. AdeRS mutations and adeB gene expression of drug efflux genes were analyzed by sequencing and qPCR, respectively. The 16S rRNA gene was used as a housekeeping gene, and the A. baumannii ATCC 19606 standard strain was also used to normalize the expression results of adeB gene. Results: Of the 97 isolates, 61 were found to be carbapenem resistant. The resistance rates of carbapenem-resistant A. baumannii (CRAB) isolates were found to be 100% for ceftazidime; 96.7% for cefepime, piperacillin-azobactam, ciprofloxacin, and trimethoprim-sulfamethoxazole; 86.8% for amikacin; and 75.4% for gentamicin and netilmicin. The significant overexpression (3.45-52.18 fold) of adeB was observed in 49 CRAB isolates, whereas less increased levels were observed in only 12 CRAB isolates (0.23-0.54 fold) and non-CRAB isolates (0.109-0.783 fold). In total, 80.3% of the CRAB isolates were positive for the adeRS genes. The p.Val120Ile change in the AdeR aminoacid sequence was determined in 42.8% of the adeB-overexpressing CRAB isolates. The p.His158Leu and p.Pro116Ser changes were found in 36.7% of these isolates. None of the non-CRAB isolates had p.Val120Ile, p.His158Leu, and p.Pro116Ser changes. In the AdeS aminoacid sequence, p.Gly293Ser, p.Leu105Phe, and His227Asp changes were most commonly observed in adeB-overexpressing CRAB isolates, whereas pGly293Ser change was detected in only 8% of the non-CRAB isolates. Conclusion: These data showed that AdeABC efflux pump overexpression (both adeB expression and AdeRS mutation) was higher than expected in our A. baumannii isolates. They were significantly associated with the AdeABC efflux system and both CRAB and MDR isolates. The overexpression of adeB and aminoacid changes in the AdeRS regions led to an increase resistance to different antibiotics; therefore, A. baumannii strains should be monitored to ensure the correct treatment, especially in nosocomial MDR. © Copyright 2019 by the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey.


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Aminoglycoside resistance, Blood stream infections, Carbapenem resistance, Efflux system genes, Proteomics


Mediterranean Journal of Infection, Microbes and Antimicrobials

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