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Sub-cellular biochemistry
2024;104 1-16.

Structures and Efflux Mechanisms of the AcrAB-TolC Pump.

Zhili Yu, Xiaodong Shi, Zhao Wang
Author Information
  1. Zhili Yu: Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
  2. Xiaodong Shi: Jiangsu Province Key Laboratory of Anesthesiology and Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  3. Zhao Wang: Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA. zhaow@bcm.edu.
PMID: 38963480 DOI: 10.1007/978-3-031-58843-3_1

Abstract

The global emergence of multidrug resistance (MDR) in gram-negative bacteria has become a matter of worldwide concern. MDR in these pathogens is closely linked to the overexpression of certain efflux pumps, particularly the resistance-nodulation-cell division (RND) efflux pumps. Inhibition of these pumps presents an attractive and promising strategy to combat antibiotic resistance, as the efflux pump inhibitors can effectively restore the potency of existing antibiotics. AcrAB-TolC is one well-studied RND efflux pump, which transports a variety of substrates, therefore providing resistance to a broad spectrum of antibiotics. To develop effective pump inhibitors, a comprehensive understanding of the structural aspect of the AcrAB-TolC efflux pump is imperative. Previous studies on this pump's structure have been limited to individual components or in vitro determination of fully assembled pumps. Recent advancements in cellular cryo-electron tomography (cryo-ET) have provided novel insights into this pump's assembly and functional mechanism within its native cell membrane environment. Here, we present a summary of the structural data regarding the AcrAB-TolC efflux pump, shedding light on its assembly pathway and operational mechanism.

Keywords

AcrAB-TolC Cryo-EM Cryo-ET Multidrug resistance RND efflux pump

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Grants

  1. R01 AI179879/NIAID NIH HHS

MeSH Term

Anti-Bacterial Agents
Drug Resistance, Multiple, Bacterial
Escherichia coli Proteins
Carrier Proteins
Bacterial Outer Membrane Proteins
Membrane Transport Proteins
Cryoelectron Microscopy
Bacterial Proteins

Chemicals

Anti-Bacterial Agents
Escherichia coli Proteins
Carrier Proteins
Bacterial Outer Membrane Proteins
Membrane Transport Proteins
AcrAB-TolC protein, E coli
Bacterial Proteins
Journal Article Review

Word Cloud

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