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Antibiotics
Special Issues
Multi-drug Efflux and Drug Permeation
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Multi-drug Efflux and Drug Permeation

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 June 2015) | Viewed by 31720

Special Issue Editor

Prof. Dr. Helen I. Zgurskaya

E-Mail Website
Guest Editor
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA
Interests: antibiotic resistance and discovery; multidrug efflux; drug permeation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Most currently available antibiotics have low efficacy against Gram-negative bacteria and Corynebacterim-Mycobacterium-Nocardia group that cause devastating infections in humans. The major factor defining the high intrinsic and acquired multidrug resistance of these pathogens is their low cell wall permeability. This permeability barrier is created by the synergistic action of two processes that occur in different membranes of bacterial cell walls. The outer membrane significantly reduces uptake of both hydrophilic and hydrophobic compounds. In the inner membrane, multidrug efflux transporters actively expel a broad range of antibiotics from the cells. This Special Issue of Antibiotics is dedicated to the topic of “Multi-drug Efflux and Drug Permeation”. Primary research manuscripts and review articles dealing with the outer membrane structure, assembly and permeation, the mechanisms and regulation of active efflux as well as current efforts in development of antibiotics that target these barriers are invited. Submitted manuscripts will be peer-reviewed to ensure that the issue contains high quality contributions.

Prof. Dr. Helen I. Zgurskaya
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. Antibiotics 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 2900 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.

Published Papers (4 papers)

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Research

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678 KiB  
Article
The Transcriptional Repressor, MtrR, of the mtrCDE Efflux Pump Operon of Neisseria gonorrhoeae Can Also Serve as an Activator of “off Target” Gene (glnE) Expression
by Paul J. T. Johnson and William M. Shafer
Antibiotics 2015, 4(2), 188-197; https://doi.org/10.3390/antibiotics4020188 - 03 Jun 2015
Cited by 11 | Viewed by 5965
Abstract
MtrR is a well-characterized repressor of the Neisseria gonorrhoeae mtrCDE efflux pump operon. However, results from a previous transcriptional profiling study suggested that MtrR also represses or activates expression of at least sixty genes outside of the mtr locus. Evidence that MtrR can [...] Read more.
MtrR is a well-characterized repressor of the Neisseria gonorrhoeae mtrCDE efflux pump operon. However, results from a previous transcriptional profiling study suggested that MtrR also represses or activates expression of at least sixty genes outside of the mtr locus. Evidence that MtrR can directly repress so-called “off target” genes has previously been reported; in particular, MtrR was shown to directly repress glnA, which encodes glutamine synthetase. In contrast, evidence for the ability of MtrR to directly activate expression of gonococcal genes has been lacking; herein, we provide such evidence. We now report that MtrR has the ability to directly activate expression of glnE, which encodes the dual functional adenyltransferase/deadenylase enzyme GlnE that modifies GlnA resulting in regulation of its role in glutamine biosynthesis. With its capacity to repress expression of glnA, the results presented herein emphasize the diverse and often opposing regulatory properties of MtrR that likely contributes to the overall physiology and metabolism of N. gonorrhoeae. Full article
(This article belongs to the Special Issue Multi-drug Efflux and Drug Permeation)
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1302 KiB  
Article
Purification of a Multidrug Resistance Transporter for Crystallization Studies
by Kamela O. Alegre and Christopher J. Law
Antibiotics 2015, 4(1), 113-135; https://doi.org/10.3390/antibiotics4010113 - 05 Mar 2015
Cited by 5 | Viewed by 9763
Abstract
Crystallization of integral membrane proteins is a challenging field and much effort has been invested in optimizing the overexpression and purification steps needed to obtain milligram amounts of pure, stable, monodisperse protein sample for crystallography studies. Our current work involves the structural and [...] Read more.
Crystallization of integral membrane proteins is a challenging field and much effort has been invested in optimizing the overexpression and purification steps needed to obtain milligram amounts of pure, stable, monodisperse protein sample for crystallography studies. Our current work involves the structural and functional characterization of the Escherichia coli multidrug resistance transporter MdtM, a member of the major facilitator superfamily (MFS). Here we present a protocol for isolation of MdtM to increase yields of recombinant protein to the milligram quantities necessary for pursuit of structural studies using X-ray crystallography. Purification of MdtM was enhanced by introduction of an elongated His-tag, followed by identification and subsequent removal of chaperonin contamination. For crystallization trials of MdtM, detergent screening using size exclusion chromatography determined that decylmaltoside (DM) was the shortest-chain detergent that maintained the protein in a stable, monodispersed state. Crystallization trials of MdtM performed using the hanging-drop diffusion method with commercially available crystallization screens yielded 3D protein crystals under several different conditions. We contend that the purification protocol described here may be employed for production of high-quality protein of other multidrug efflux members of the MFS, a ubiquitous, physiologically and clinically important class of membrane transporters. Full article
(This article belongs to the Special Issue Multi-drug Efflux and Drug Permeation)
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Review

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2452 KiB  
Review
Focus on the Outer Membrane Factor OprM, the Forgotten Player from Efflux Pumps Assemblies
by Gilles Phan, Martin Picard and Isabelle Broutin
Antibiotics 2015, 4(4), 544-566; https://doi.org/10.3390/antibiotics4040544 - 12 Nov 2015
Cited by 14 | Viewed by 7289
Abstract
Antibiotics have been used extensively during several decades and we are now facing the emergence of multidrug resistant strains. It has become a major public concern, urging the need to discover new strategies to combat them. Among the different ways used by bacteria [...] Read more.
Antibiotics have been used extensively during several decades and we are now facing the emergence of multidrug resistant strains. It has become a major public concern, urging the need to discover new strategies to combat them. Among the different ways used by bacteria to resist antibiotics, the active efflux is one of the main mechanisms. In Gram-negative bacteria the efflux pumps are comprised of three components forming a long edifice crossing the complete cell wall from the inside to the outside of the cell. Blocking these pumps would permit the restoration of the effectiveness of the current antibiotherapy which is why it is important to increase our knowledge on the different proteins involved in these complexes. A tremendous number of experiments have been performed on the inner membrane protein AcrB from Escherichia coli and, to a lesser extent, the protein partners forming the AcrAB-TolC pump, but less information is available concerning the efflux pumps from other virulent Gram-negative bacteria. The present review will focus on the OprM outer membrane protein from the MexAB-OprM pump of Pseudomonas aeruginosa, highlighting similarities and differences compare to the archetypal AcrAB-TolC in terms of structure, function, and assembly properties. Full article
(This article belongs to the Special Issue Multi-drug Efflux and Drug Permeation)
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697 KiB  
Review
Multidrug Efflux Systems in Microaerobic and Anaerobic Bacteria
by Zeling Xu and Aixin Yan
Antibiotics 2015, 4(3), 379-396; https://doi.org/10.3390/antibiotics4030379 - 28 Aug 2015
Cited by 10 | Viewed by 8173
Abstract
Active drug efflux constitutes an important mechanism of antibiotic and multidrug resistance in bacteria. Understanding the distribution, expression, and physiological functions of multidrug efflux pumps, especially under physiologically and clinically relevant conditions of the pathogens, is the key to combat drug resistance. In [...] Read more.
Active drug efflux constitutes an important mechanism of antibiotic and multidrug resistance in bacteria. Understanding the distribution, expression, and physiological functions of multidrug efflux pumps, especially under physiologically and clinically relevant conditions of the pathogens, is the key to combat drug resistance. In animal hosts, most wounded, infected and inflamed tissues display low oxygen tensions. In this article, we summarize research development on multidrug efflux pumps in the medicinally relevant microaerobic and anaerobic pathogens and their implications in the effort to combat drug-resistant infections. Full article
(This article belongs to the Special Issue Multi-drug Efflux and Drug Permeation)
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