scholarly journals Multidrug efflux systems in Gram-negative bacteria

2004 ◽  
Vol 35 (1-2) ◽  
Author(s):  
Maria Aparecida Scatamburlo Moreira ◽  
Edmar Chartone de Souza ◽  
Célia Alencar de Moraes
Keyword(s):  
Gram Negative Bacteria ◽  
Multidrug Efflux ◽  
Gram Negative

scholarly journals Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their synergism with the outer membrane barrier

2018 ◽  
Vol 169 (7-8) ◽  
pp. 351-356 ◽  
Author(s):  
Helen I. Zgurskaya ◽  
Valentin V. Rybenkov ◽  
Ganesh Krishnamoorthy ◽  
Inga V. Leus
Keyword(s):  
Outer Membrane ◽  
Efflux Pumps ◽  
Gram Negative Bacteria ◽  
Multidrug Efflux ◽  
Gram Negative ◽  
Multidrug Efflux Pumps ◽  
Membrane Barrier

scholarly journals Chimeric Analysis of the Multicomponent Multidrug Efflux Transporters from Gram-Negative Bacteria

2002 ◽  
Vol 184 (23) ◽  
pp. 6499-6507 ◽  
Author(s):  
Elena B. Tikhonova ◽  
Quiju Wang ◽  
Helen I. Zgurskaya
Keyword(s):  
Gram Negative Bacteria ◽  
Bacterial Cells ◽  
Multidrug Efflux ◽  
Structural Determinants ◽  
Gram Negative ◽  
E Coli ◽  
Multidrug Transporters ◽  
Cytoplasmic Membranes ◽  
Hybrid Genes ◽  
Rnd Transporters

ABSTRACT Many multidrug transporters from gram-negative bacteria belong to the resistance-nodulation-cell division (RND) superfamily of transporters. RND-type multidrug transporters have an extremely broad substrate specificity and protect bacterial cells from the actions of antibiotics on both sides of the cytoplasmic membrane. They usually function as three-component assemblies spanning the outer and cytoplasmic membranes and the periplasmic space of gram-negative bacteria. The structural determinants of RND transporters responsible for multidrug recognition and complex assembly remain unknown. We constructed chimeric RND transporters composed of N-terminal residues of AcrB and C-terminal residues of MexB, the major RND-type transporters from Escherichia coli and Pseudomonas aeruginosa, respectively. The assembly of complexes and multidrug efflux activities of chimeric transporters were determined by coexpression of hybrid genes either with AcrA, the periplasmic component of the AcrAB transporter from E. coli, or with MexA and OprM, the accessory proteins of the MexAB-OprM pump from P. aeruginosa. We found that the specificity of interaction with the corresponding periplasmic component is encoded in the T60-V612 region of transporters. Our results also suggest that the large periplasmic loops of RND-type transporters are involved in multidrug recognition and efflux.

MsbA: an ABC transporter paradigm

2021 ◽  
Author(s):  
Christian Bonifer ◽  
Clemens Glaubitz
Keyword(s):  
Abc Transporters ◽  
Atp Hydrolysis ◽  
3D Structure ◽  
Membrane Integrity ◽  
Current Data ◽  
Gram Negative Bacteria ◽  
Multidrug Efflux ◽  
Gram Negative ◽  
Multidrug Efflux Pumps ◽  
Future Work

ATP-binding cassette (ABC) transporters play an important role in various cellular processes. They display a similar architecture and share a mechanism which couples ATP hydrolysis to substrate transport. However, in the light of current data and recent experimental progress, this protein superfamily appears as multifaceted as their broad substrate range. Among the prokaryotic ABC transporters, MsbA can serve as a paradigm for research in this field. It is located in the inner membrane of Gram-negative bacteria and functions as a floppase for the lipopolysaccharide (LPS) precursor core-LPS, which is involved in the biogenesis of the bacterial outer membrane. While MsbA shows high similarity to eukaryotic ABC transporters, its expression in Gram-negative bacteria makes it conveniently accessible for many experimental approaches from spectroscopy to 3D structure determination. As an essential protein for bacterial membrane integrity, MsbA has also become an attractive target for the development of novel antibiotics. Furthermore, it serves as a model for multidrug efflux pumps. Here we provide an overview of recent findings and their relevance to the field, highlight the potential of methods such as solid-state NMR and EPR spectroscopy and provide a perspective for future work.

scholarly journals Achromobacter Infections and Treatment Options

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Burcu Isler ◽  
Timothy J. Kidd ◽  
Adam G. Stewart ◽  
Patrick Harris ◽  
David L. Paterson
Keyword(s):  
Treatment Options ◽  
Carbapenem Resistance ◽  
Adverse Outcomes ◽  
Gram Negative Bacteria ◽  
Rare Occurrence ◽  
Multidrug Efflux ◽  
Gram Negative ◽  
Multidrug Efflux Pumps ◽  
Number Of Patients ◽  
New Antibiotics

ABSTRACT Achromobacter is a genus of nonfermenting Gram-negative bacteria under order Burkholderiales. Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g., most cephalosporins, aztreonam, and aminoglycosides), and are increasingly acquiring resistance to carbapenems. Carbapenem resistance is mainly caused by multidrug efflux pumps and metallo-β-lactamases, which are not expected to be overcome by new β-lactamase inhibitors. Among the other new antibiotics, cefiderocol, and eravacycline were used as salvage therapy for a limited number of patients with Achromobacter infections. In this article, we aim to give an overview of the antimicrobial resistance in Achromobacter species, highlighting the possible place of new antibiotics in their treatment.

scholarly journals Genetic Variability of the AcrAB-TolC Multidrug Efflux Pump Underlies SkQ1 Resistance in Gram-Negative Bacteria

Acta Naturae ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 93-98 ◽  
Author(s):  
P. A. Nazarov ◽  
E. A. Kotova ◽  
V. P. Skulachev ◽  
Y. N. Antonenko
Keyword(s):  
Protein Sequence ◽  
Efflux Pump ◽  
Accessory Protein ◽  
Gram Negative Bacteria ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Chloramphenicol Resistance ◽  
Gram Negative ◽  
E Coli ◽  
Transporter Protein

SkQ1, a novel antibiotic targeting bacterial bioenergetics, is highly effective against both gram-positive and gram-negative bacteria. However, some gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, are highly resistant to it. In different gram-negative bacteria, this resistance is associated with the identity of their AcrB transporter protein sequence with the sequence of the AcrB protein from E. coli. SkQ1 is expelled from E. coli cells by the AcrAB-TolC multidrug efflux pump. In this study, we demonstrate that SkQ1 resistance in E. coli, in contrast to chloramphenicol resistance, does not depend on the presence of the multidrug efflux pump accessory protein AcrZ.

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