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Microorganisms
Special Issues
Multidrug Efflux Pumps
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Multidrug Efflux Pumps

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (1 September 2020) | Viewed by 12625

Special Issue Editor

Prof. Dr. Akihito Yamaguchi

E-Mail Website
Guest Editor
Laboratory of Cell Membrane Structural Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan
Interests: multidrug efflux pumps; multidrug recognition; AcrB; MexB; MexY; RND; exporter; transporter; multisite-binding; X-ray crystal structure; multidrug resistance; active barrier; evolution

Special Issue Information

Dear Colleagues,

Multidrug transport is a transport without recognition. RND-type multidrug exporters transport hydrophobic and amphiphilic compounds by the functional rotation mechanism of trimers with peristaltic motion of intracellular channels and pockets through the multiple entrances. Although they have multidrug-binding sites in the proximal and distal pockets, the binding structures reflect the evolutionally-acquired enhanced transport for specific compounds. The range of their substrate recognition spectrum has not been expanded during their evolution. Evolution gives enhanced ability for transport of specific compounds, the extrusions of which are favorable for survival in the living environment. Multidrug efflux itself is a priori-installed characteristics of a multidrug transporter, that is, a transport without recognition. Substrates are selected only by their accessibility to the entrances depending on their physicochemical properties, and they are unidirectionally sent by peristaltic motion of the channels as a simply occluded form until the exit. Multidrug transporter is an active barrier essential for cell membrane barrier function to compensate for the fact that lipid bilayers have a weak barrier function to hydrophobic and amphiphilic compounds. That is the conclusion of our long-term studies to reveal the substrate-binding structures of multidrug efflux transporters and their evolution.

Prof. Dr. Akihito Yamaguchi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multidrug efflux pumps
  • multidrug recognition
  • AcrB
  • MexB
  • MexY
  • RND
  • exporter
  • transporter
  • multisite-binding
  • X-ray crystal structure
  • multidrug resistance
  • active barrier
  • evolution

Published Papers (2 papers)

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Research

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21 pages, 4434 KiB  
Article
Cryo-EM Structure and Molecular Dynamics Analysis of the Fluoroquinolone Resistant Mutant of the AcrB Transporter from Salmonella
by Rachel M. Johnson, Chiara Fais, Mayuriben Parmar, Harish Cheruvara, Robert L. Marshall, Sophie J. Hesketh, Matthew C. Feasey, Paolo Ruggerone, Attilio V. Vargiu, Vincent L. G. Postis, Stephen P. Muench and Vassiliy N. Bavro
Microorganisms 2020, 8(6), 943; https://doi.org/10.3390/microorganisms8060943 - 23 Jun 2020
Cited by 22 | Viewed by 5232
Abstract
Salmonella is an important genus of Gram-negative pathogens, treatment of which has become problematic due to increases in antimicrobial resistance. This is partly attributable to the overexpression of tripartite efflux pumps, particularly the constitutively expressed AcrAB-TolC. Despite its clinical importance, the structure of [...] Read more.
Salmonella is an important genus of Gram-negative pathogens, treatment of which has become problematic due to increases in antimicrobial resistance. This is partly attributable to the overexpression of tripartite efflux pumps, particularly the constitutively expressed AcrAB-TolC. Despite its clinical importance, the structure of the Salmonella AcrB transporter remained unknown to-date, with much of our structural understanding coming from the Escherichia coli orthologue. Here, by taking advantage of the styrene maleic acid (SMA) technology to isolate membrane proteins with closely associated lipids, we report the very first experimental structure of Salmonella AcrB transporter. Furthermore, this novel structure provides additional insight into mechanisms of drug efflux as it bears the mutation (G288D), originating from a clinical isolate of Salmonella Typhimurium presenting an increased resistance to fluoroquinolones. Experimental data are complemented by state-of-the-art molecular dynamics (MD) simulations on both the wild type and G288D variant of Salmonella AcrB. Together, these reveal several important differences with respect to the E. coli protein, providing insights into the role of the G288D mutation in increasing drug efflux and extending our understanding of the mechanisms underlying antibiotic resistance. Full article
(This article belongs to the Special Issue Multidrug Efflux Pumps)
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Review

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20 pages, 1710 KiB  
Review
Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps
by Sanath Kumar, Manjusha Lekshmi, Ammini Parvathi, Manisha Ojha, Nicholas Wenzel and Manuel F. Varela
Microorganisms 2020, 8(2), 266; https://doi.org/10.3390/microorganisms8020266 - 16 Feb 2020
Cited by 60 | Viewed by 6965
Abstract
Pathogenic microorganisms that are multidrug-resistant can pose severe clinical and public health concerns. In particular, bacterial multidrug efflux transporters of the major facilitator superfamily constitute a notable group of drug resistance mechanisms primarily because multidrug-resistant pathogens can become refractory to antimicrobial agents, thus [...] Read more.
Pathogenic microorganisms that are multidrug-resistant can pose severe clinical and public health concerns. In particular, bacterial multidrug efflux transporters of the major facilitator superfamily constitute a notable group of drug resistance mechanisms primarily because multidrug-resistant pathogens can become refractory to antimicrobial agents, thus resulting in potentially untreatable bacterial infections. The major facilitator superfamily is composed of thousands of solute transporters that are related in terms of their phylogenetic relationships, primary amino acid sequences, two- and three-dimensional structures, modes of energization (passive and secondary active), and in their mechanisms of solute and ion translocation across the membrane. The major facilitator superfamily is also composed of numerous families and sub-families of homologous transporters that are conserved across all living taxa, from bacteria to humans. Members of this superfamily share several classes of highly conserved amino acid sequence motifs that play essential mechanistic roles during transport. The structural and functional importance of multidrug efflux pumps that belong to the major facilitator family and that are harbored by Gram-negative and -positive bacterial pathogens are considered here. Full article
(This article belongs to the Special Issue Multidrug Efflux Pumps)
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