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Ader-ades mutations & overexpression of the AdeABC efflux system in ciprofloxacin-resistant acinetobacter baumannii clinical isolates

Lari, A.R. and Ardebili, A. and Hashemi, A. (2018) Ader-ades mutations & overexpression of the AdeABC efflux system in ciprofloxacin-resistant acinetobacter baumannii clinical isolates. Indian Journal of Medical Research, 147 (April). pp. 413-421.

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Abstract

Background & objectives: Overexpression of efflux pumps is a cause of acquired resistance to fluoroquinolones in Acinetobacter baumannii. The present study was done to investigate the presence and overexpression of AdeABC efflux system and to analyze the sequences of AdeR-AdeS regulatory system in ciprofloxacin-resistant A. baumannii isolates. Methods: Susceptibility of 50 clinical A. baumannii isolates to ciprofloxacin, imipenem, ceftazidime, cefepime and gentamicin antimicrobials was evaluated by agar dilution method. Isolates were screened for the evidence of active efflux pump. Isolates were also examined for adeR-adeS and adeB efflux genes by polymerase chain reaction (PCR). The adeR and adeS regulatory genes were sequenced to detect amino acid substitutions. Expression of adeB was evaluated by quantitative reverse-transcriptase PCR. Results: There were high rates of resistance to ciprofloxacin (88), ceftazidime (88), cefepime (74) and imipenem (72) and less resistance rate to gentamicin (64). Phenotypic assay showed involvement of active efflux in decreased susceptibility to ciprofloxacin among 16 isolates. The 12.27-fold increase and 4.25-fold increase were found in adeB expression in ciprofloxacin-full-resistant and ciprofloxacin-intermediate-resistant isolates, respectively. Several effective mutations, including A91V, A136V, L192R, A94V, G103D and G186V, were detected in some domains of AdeR-AdeS regulators in the overexpressed ciprofloxacin-resistant isolates. Interpretation & conclusions: The results of this study indicated that overexpression of the AdeABC efflux pump was important to reduce susceptibility to ciprofloxacin and cefepime in A. baumannii that, in turn, could be triggered by alterations in the AdeR-AdeS two-component system. However, gene expression alone does not seem adequate to explain multidrug resistance phenomenon. These results could help plan improved active efflux pump inhibitors. © 2018, Indian Council of Medical Research. All rights reserved.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: carbonyl cyanide chlorophenylhydrazone; cefepime; ceftazidime; ciprofloxacin; imipenem; RNA 16S, Acinetobacter baumannii; adeB gene; adeR gene; adeS gene; agar dilution; amino acid substitution; antibiotic resistance; antibiotic sensitivity; Article; bacterial strain; bacterium isolate; Escherichia coli; gene; gene locus; gene mutation; gene overexpression; MIC50; MIC90; nonhuman; nucleotide sequence; phenotype; Pseudomonas aeruginosa; real time polymerase chain reaction; reverse transcription polymerase chain reaction; sequence alignment; single nucleotide polymorphism
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: UNSPECIFIED
Depositing User: GOUMS
Date Deposited: 29 Sep 2018 07:36
Last Modified: 29 Sep 2018 07:36
URI: http://eprints.goums.ac.ir/id/eprint/9700

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