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Authors Zhang Y, Li Z, He X, Ding F, Wu W, Luo Y, Fan B, Cao H
Received 11 September 2017
Accepted for publication 23 December 2017
Published 29 March 2018 Volume 2018:11 Pages 457—467
DOI https://doi.org/10.2147/IDR.S151423
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Dr Sahil Khanna
Purpose: Acinetobacter baumannii is an
important pathogen in the nosocomial infections worldwide. Combining with carbapenemases,
efflux pumps and outer membrane proteins (OMPs) have been thought to affect the
development of carbapenem resistance in A. baumannii . This
study aimed to investigate the contributions of different efflux pumps and OMPs
in developing carbapenem resistance in a clinical isolate of A. baumannii and reveal
the possible mechanism of overproduction of main efflux pumps.
Patients and
methods: In this study, an
imipenem-susceptible clinical isolate was identified as A. baumannii and named SZE.
Several common carbapenemases were detected by polymerase chain reaction (PCR).
Imipenem-selected mutants were selected from SZE by serial subcultivations on
Mueller–Hinton agar, and the minimum inhibitory concentration (MIC) was
detected. Gene expressions of four families of efflux pumps, five OMPs,
and bla OXA-51 were determined by reverse transcription quantitative PCR, and
comparisons were made between SZE strain and the imipenem-selected mutants.
The adeRS system in SZE and its
mutant was sequenced and aligned.
Results: Under consecutive imipenem-selected stress, the MIC to imipenem
increased gradually from 0.125 μg/mL to 8 μg/mL. The effect of resistance
inducement was almost neutralized when treated with an efflux pump inhibitor.
The expression of efflux pumps, adeB , adeG , and adeJ , was increased by 6.9-, 4.0-,
and 2.1-fold in mutants, respectively, compared to SZE. A single mutation (G to
A) at position 58 was detected in the regulatory adeRS system and possibly
upregulated the adeB expression,
and then affected the carbapenem resistance in A.
baumannii strains.
Conclusion: In conclusion, under consecutive imipenem-selected stress in vitro, A. baumannii strain
evolved the ability to reduce susceptibility to a variety of antimicrobials by
overproduction of efflux pumps. Especially, the resistance-nodulation-cell
division super family and a nucleotide mutant in adeRS regulating system
caused the overexpression of adeABC .
Keywords: Acinetobacter
baumannii , efflux pump, multidrug resistance, imipenem,
outer membrane protein