Abstract
Multidrug efflux pumps play an important role in antimicrobial
resistance and pathogenicity in bacteria. Here, we report
the functional characterization of the RND (resistance-nodulation-
division) efflux pump, AcrAB, in Acinetobacter nosocomialis.
An in silico analysis revealed that homologues of the
AcrAB efflux pump, comprising AcrA and AcrB, are widely
distributed among different bacterial species. Deletion of acrA
and/or acrB genes led to decreased biofilm/pellicle formation
and reduced antimicrobial resistance in A. nosocomialis. RNA
sequencing and mRNA expression analyses showed that expression
of acrA/B was downregulated in a quorum sensing
(QS) regulator (anoR)-deletion mutant, indicating transcriptional
activation of the acrAB operon by AnoR in A. nosocomialis.
Bioassays showed that secretion of N-acyl homoserine
lactones (AHLs) was unaffected in acrA and acrB deletion
mutants; however, AHL secretion was limited in a deletion
mutant of acrR, encoding the acrAB regulator, AcrR.
An in silico analysis indicated the presence of AcrR-binding
motifs in promoter regions of anoI (encoding AHL synthase)
and anoR. Specific binding of AcrR was confirmed by electrophoretic
mobility shift assays, which revealed that AcrR
binds to positions -214 and -217 bp upstream of the translational
start sites of anoI and anoR, respectively, demonstrating
transcriptional regulation of these QS genes by AcrR.
The current study further addresses the possibility that AcrAB
is controlled by the osmotic stress regulator, OmpR, in A.
nosocomialis. Our data demonstrate that the AcrAB efflux
pump plays a crucial role in biofilm/pellicle formation and
antimicrobial resistance in A. nosocomialis, and is under the
transcriptional control of a number of regulators. In addition,
the study emphasizes the interrelationship of QS and AcrAB
efflux systems in A. nosocomialis.
Citations
Citations to this article as recorded by

- Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference to Acinetobacter baumannii
Kira M. Zack, Trent Sorenson, Suresh G. Joshi
Pathogens.2024; 13(3): 197. CrossRef - Lysine Trimethylation in Planktonic and Pellicle Modes of Growth in Acinetobacter baumannii
Nicolas Nalpas, Takfarinas Kentache, Emmanuelle Dé, Julie Hardouin
Journal of Proteome Research.2023; 22(7): 2339. CrossRef - The Mechanism of Tigecycline Resistance in Acinetobacter baumannii Revealed by Proteomic and Genomic Analysis
Cunwei Liu, Lei Wang, Ping Wang, Di Xiao, Qinghua Zou
International Journal of Molecular Sciences.2023; 24(10): 8652. CrossRef - Antimicrobial photodynamic therapy against oral biofilm: influencing factors, mechanisms, and combined actions with other strategies
Yijun Li, Guanwen Sun, Jingchan Xie, Suli Xiao, Chen Lin
Frontiers in Microbiology.2023;[Epub] CrossRef - The multifaceted genusAcinetobacter: from infection to bioremediation
Ujwal Dahal, Karan Paul, Shelly Gupta
Journal of Applied Microbiology.2023;[Epub] CrossRef - Efflux pumps and microbial biofilm formation
Mahdyeh Neghabi Hajiagha, Hossein Samadi Kafil
Infection, Genetics and Evolution.2023; 112: 105459. CrossRef - Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria
Ronit Vogt Sionov, Doron Steinberg
Microorganisms.2022; 10(6): 1239. CrossRef - Evidence for Complex Interplay between Quorum Sensing and Antibiotic Resistance in Pseudomonas aeruginosa
Rakesh Sikdar, Mikael H. Elias, Giordano Rampioni
Microbiology Spectrum.2022;[Epub] CrossRef - Update on Multidrug Resistance Efflux Pumps in Acinetobacter spp.
Vanessa Kornelsen, Ayush Kumar
Antimicrobial Agents and Chemotherapy.2021;[Epub] CrossRef - Orthopedic Implant-Related Biofilm Pathophysiology: A Review of the Literature
Meletis Rozis, Dimitrios S Evangelopoulos, Spyros G Pneumaticos
Cureus.2021;[Epub] CrossRef - The impact of cell structure, metabolism and group behavior for the survival of bacteria under stress conditions
Xinyi Zhang, Zhendong Li, Shengmei Pang, Boyu Jiang, Yang Yang, Qiangde Duan, Guoqiang Zhu
Archives of Microbiology.2021; 203(2): 431. CrossRef