Multidrug ABC transporters in bacteria

Orelle, Cédric; Mathieu, Khadija; Jault, Jean‐Michel

doi:10.1016/j.resmic.2019.06.001

Cited by 103 publications

(61 citation statements)

References 175 publications

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“…Based on these considerations, both domain arrangement and cluster analysis supported YbhFSR as a single-drug efflux transporter. Subsequently, we knocked out and overexpressed the ybhF gene of the ATP-binding domain in the YbhFSR transporter, which destroyed the integrity of the YbhFSR transporter and affected its function (Orelle et al, 2019). The MIC assay confirmed YbhFSR efflux tetracyclines, EB, and Hoechst33342.…”

Section: Discussionmentioning

confidence: 98%

“…The presence of bacterial drug efflux transporters is a problem for treatment of bacterial infections because efflux pumps can transport drugs or other substrates outside of the cells and thereby reduce the concentration of drugs (Orelle et al, 2019). Most multidrug efflux pumps of eukaryotes belong to the ATP-binding cassette (ABC) family of transporters, while in prokaryotes, five superfamilies of multi-drug efflux pumps can cause antibiotic resistance (Li et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…ATP-binding cassette proteins, an ancient and large family, are widely distributed in almost all species from bacteria to yeast, nematodes, fruit flies, plants, and mammals (Davidson et al, 2008;Moussatova et al, 2008;Eitinger et al, 2011;Teichmann et al, 2017). The ABC transporters have a similar topology, with two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs) (Orelle et al, 2019). The NBD is located in the cytoplasmic membrane and uses the energy released by ATP hydrolysis to extrude pump substrates through the membrane (Dean et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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A Putative Efflux Transporter of the ABC Family, YbhFSR, in Escherichia coli Functions in Tetracycline Efflux and Na+(Li+)/H+ Transport

et al. 2020

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ATP-binding cassette transporters are ubiquitous in almost all organisms. The Escherichia coli genome is predicted to encode 69 ABC transporters. Eleven of the ABC transporters are presumed to be exporters, of which seven are possible drug export transporters. There has been minimal research on the function of YbhFSR, which is one of the putative drug resistance exporters. In this study, the ybhF gene of this transporter was characterized. Overexpression and knockout strains of ybhF were constructed. The ATPase activity of YbhF was studied using the malachite green assay, and the efflux abilities of knockout strains were demonstrated by using ethidium bromide (EB) as a substrate. The substrates of YbhFSR efflux, examined with the minimum inhibitory concentration (MIC), were determined to be tetracycline, oxytetracycline, chlortetracycline, doxycycline, EB, and Hoechst33342. Furthermore, tetracycline and EB efflux and accumulation experiments confirmed that the substrates of YbhFSR were tetracyclines and EB. The MIC assay and the fluorescence test results showed that tetracyclines are likely to be the major antibiotic substrate of YbhFSR. The existence of the signature NatA motif suggested that YbhFSR may also function as a Na + /H + transporter. Overexpression of YbhF in E. coli KNabc lacking crucial Na + /H + transporters conferred tolerance to NaCl, LiCl, and an alkaline pH. Together, the results showed that YbhFSR exhibited dual functions as a drug efflux pump and a Na + (Li +)/H + antiporter.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Putative Efflux Transporter of the ABC Family, YbhFSR, in Escherichia coli Functions in Tetracycline Efflux and Na+(Li+)/H+ Transport

et al. 2020

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“…For example, eukaryotic homodimeric TAPL complex undergoes ATP hydrolysis that are highly uncoupled from substrate transport (20-100 ATP hydrolyzed per translocated peptide) consistent with a high degree of futile hydrolysis cycles 14 while the heterodimeric TAP complex shows a strict coupling between peptide transport and ATP hydrolysis 13 . Whether futile, wasteful, expenditure of ATP is an intrinsic feature of ABC transporters or an artefactual consequence of the manipulation of detergent-solubilized proteins is a matter of debate 27 . We show here that at steady state, MacAB-TolC transports 65 nmol roxithromycin per mg MacB and per minute at the expense of 20 nmol ATP hydrolyzed, meaning that, in our hands, MacAB is a very efficient transporter.…”

Section: Discussionmentioning

confidence: 99%

Quantum dot probes for the quantitative study of drug transport by the MacAB TolC efflux pump in lipid scaffolds

Souabni

Santos

Cece

et al. 2020

Preprint

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ABC tripartite efflux pumps are macromolecular membrane protein machineries that expel a large variety of drugs and export virulence factors from Gram negative bacteria. Using a lipid scaffold mimicking the two-membrane environment of the transporter and designing spectroscopic conditions allowing the monitoring of both ATP hydrolysis and substrate transport in real time, we show that MacAB-TolC accommodates transport and energy consumption with high coupling efficiency.

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“…P46 might well be a highaffinity sugar-recognizing subunit from an as yet uncharacterized ABC transporter system that is likely to be composed of the protein products (in M. hyopneumoniae strain J) of the MHJ_RS02730 and MHJ_RS02735 genes, which are immediately downstream of the P46 coding gene and are predicted to be an ATP-binding protein and a permease, respectively. The number of studies of ABC transporters, which in M. hyopneumoniae represent $85% of the membrane-transport systems in the cell (Nicolá s et al, 2007), has increased rapidly in recent years (Orelle et al, 2019;Ford & Beis, 2019). The immunogenic properties of ABC transporters and their roles in virulence make them promising vaccine candidates and antimicrobial targets.…”

Section: Introductionmentioning

confidence: 99%

Structure of P46, an immunodominant surface protein fromMycoplasma hyopneumoniae: interaction with a monoclonal antibody

Guasch

Montané²,

Moros³

et al. 2020

Acta Crystallogr D Struct Biol

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Mycoplasma hyopneumoniae is a prokaryotic pathogen that colonizes the respiratory ciliated epithelial cells in swine. Infected animals suffer respiratory lesions, causing major economic losses in the porcine industry. Characterization of the immunodominant membrane-associated proteins from M. hyopneumoniae may be instrumental in the development of new therapeutic approaches. Here, the crystal structure of P46, one of the main surface-antigen proteins, from M. hyopneumoniae is presented and shows N-and C-terminal / domains connected by a hinge. The structures solved in this work include a ligand-free open form of P46 (3.1 Å resolution) and two ligand-bound structures of P46 with maltose (2.5 Å resolution) and xylose (3.5 Å resolution) in open and closed conformations, respectively. The ligand-binding site is buried in the cleft between the domains at the hinge region. The two domains of P46 can rotate with respect to each other, giving open or closed alternative conformations. In agreement with this structural information, sequence analyses show similarities to substrate-binding members of the ABC transporter superfamily, with P46 facing the extracellular side as a functional subunit. In the structure with xylose, P46 was also bound to a high-affinity (K d = 29 nM) Fab fragment from a monoclonal antibody, allowing the characterization of a structural epitope in P46 that exclusively involves residues from the C-terminal domain. The Fab structure in the complex with P46 shows only small conformational rearrangements in the six complementarity-determining regions (CDRs) with respect to the unbound Fab (the structure of which is also determined in this work at 1.95 Å resolution). The structural information that is now available should contribute to a better understanding of sugar nutrient intake by M. hyopneumoniae. This information will also allow the design of protocols and strategies for the generation of new vaccines against this important swine pathogen. research papers Acta Cryst. (2020). D76, 418-427 Guasch et al. P46 from Mycoplasma hyopneumoniae 419

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Multidrug ABC transporters in bacteria

Cited by 103 publications

References 175 publications

A Putative Efflux Transporter of the ABC Family, YbhFSR, in Escherichia coli Functions in Tetracycline Efflux and Na+(Li+)/H+ Transport

A Putative Efflux Transporter of the ABC Family, YbhFSR, in Escherichia coli Functions in Tetracycline Efflux and Na+(Li+)/H+ Transport

Quantum dot probes for the quantitative study of drug transport by the MacAB TolC efflux pump in lipid scaffolds

Structure of P46, an immunodominant surface protein fromMycoplasma hyopneumoniae: interaction with a monoclonal antibody

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