J Bacteriol Virol.  2019 Mar;49(1):1-11. 10.4167/jbv.2019.49.1.1.

RND efflux pump systems in Acinetobacter, with special emphasis on their role in quorum sensing

Affiliations
  • 1Department of Microbiology and Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea 35015. choich@cnu.ac.kr
  • 2Department of Nanobiomedical Science, Dankook University, Cheonan, South Korea 31116.

Abstract

Acinetobacter is an important opportunistic, multidrug resistant pathogen causing majority of nosocomial infections worldwide. The multidrug resistance is attributed by a plethora of efflux pumps and the overexpression of the same mediates export of antimicrobial agents. Quorum sensing (QS) is the cell-to-cell communication system in which bacteria produces specific signaling molecules which are transported out to the surrounding environment to communicate with other bacterial cells. It has been noticed that multidrug efflux pumps like resistance-nodulation-cell division (RND) efflux pumps play an important role in QS by exporting these signaling molecules. This review discusses various RND efflux pumps and the current understanding of the interrelationship of RND efflux pumps and QS in Acinetobacter spp. Studies demonstrate that RND efflux pumps could be considered as potential targets to block QS thereby reducing pathogenesis and antibiotic resistance. The known RND efflux pump-mediated quorum quenching strategies for Acinetobacter and other bacterial strains are discussed in detail. Finally, the prospective quorum quenching strategies targeting the transcriptional regulators of RND efflux pumps to inhibit multidrug efflux pumps are addressed.

Keyword

Acinetobacter; RND efflux pumps; quorum sensing; quorum quenching

MeSH Terms

Acinetobacter*
Anti-Infective Agents
Bacteria
Cross Infection
Drug Resistance, Microbial
Drug Resistance, Multiple
Prospective Studies
Quorum Sensing*
Anti-Infective Agents

Figure

  • Figure 1. Schematic representation of quorum quenching strategies targeting multidrug efflux pumps, considering A. nosocomialis as a representative strain. anol and anoR genes encode AHL signal synthase and AHL receptor/activator protein respectively. The efflux pump inhibitors binding to the efflux pumps inhibit the export of AHLs to the external environment blocking the quorum sensing system. The nearby bacterial cells are deprived of AHLs to be transported into the cells disrupting the formation of AnoR-AHL complex, thus preventing the binding of AnoR-AHL to the promoter regions of target genes including those for biofilm formation and virulence. The acrA and acrB efflux pump genes are shown as examples of multidrug efflux pump genes in A. nosocomialis. The biomolecules which target the transcriptional regulators of efflux pump genes inhibit the expression of these genes leading to the disruption of the quorum sensing system.


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