Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE
Abstract Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organis...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-16995-x |
| _version_ | 1818344288496386048 |
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| author | Giulia Tamburrino Salomé Llabrés Owen N. Vickery Samantha J. Pitt Ulrich Zachariae |
| author_facet | Giulia Tamburrino Salomé Llabrés Owen N. Vickery Samantha J. Pitt Ulrich Zachariae |
| author_sort | Giulia Tamburrino |
| collection | DOAJ |
| description | Abstract Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. In Neisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings and in silico techniques. Our in vitro results show that MtrE can be regulated by periplasmic binding events and that the interaction between MtrE and MtrC is sufficient to stabilize this complex in an open state. In contrast to other efflux conduits, the open complex only displays a slight preference for cations. The maximum conductance we obtain in the in vitro recordings is comparable to that seen in our computational electrophysiology simulations conducted on the MtrE crystal structure, indicating that this state may reflect a physiologically relevant open conformation of MtrE. Our results suggest that the MtrC/E binding interface is an important modulator of MtrE function, which could potentially be targeted by new efflux inhibitors. |
| first_indexed | 2024-12-13T16:44:06Z |
| format | Article |
| id | doaj.art-14bb12e59497474ea99ab84771bb053c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:44:06Z |
| publishDate | 2017-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-14bb12e59497474ea99ab84771bb053c2022-12-21T23:38:13ZengNature PortfolioScientific Reports2045-23222017-12-017111010.1038/s41598-017-16995-xModulation of the Neisseria gonorrhoeae drug efflux conduit MtrEGiulia Tamburrino0Salomé Llabrés1Owen N. Vickery2Samantha J. Pitt3Ulrich Zachariae4Computational Biology, School of Life Sciences, University of DundeeComputational Biology, School of Life Sciences, University of DundeeComputational Biology, School of Life Sciences, University of DundeeSchool of Medicine, University of St AndrewsComputational Biology, School of Life Sciences, University of DundeeAbstract Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. In Neisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings and in silico techniques. Our in vitro results show that MtrE can be regulated by periplasmic binding events and that the interaction between MtrE and MtrC is sufficient to stabilize this complex in an open state. In contrast to other efflux conduits, the open complex only displays a slight preference for cations. The maximum conductance we obtain in the in vitro recordings is comparable to that seen in our computational electrophysiology simulations conducted on the MtrE crystal structure, indicating that this state may reflect a physiologically relevant open conformation of MtrE. Our results suggest that the MtrC/E binding interface is an important modulator of MtrE function, which could potentially be targeted by new efflux inhibitors.https://doi.org/10.1038/s41598-017-16995-x |
| spellingShingle | Giulia Tamburrino Salomé Llabrés Owen N. Vickery Samantha J. Pitt Ulrich Zachariae Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE Scientific Reports |
| title | Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE |
| title_full | Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE |
| title_fullStr | Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE |
| title_full_unstemmed | Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE |
| title_short | Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE |
| title_sort | modulation of the neisseria gonorrhoeae drug efflux conduit mtre |
| url | https://doi.org/10.1038/s41598-017-16995-x |
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