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Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE

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Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE. / Tamburrino, Giulia ; Llabrés, Salomé; Vickery, Owen; Pitt, Samantha Jane; Zachariae, Ulrich.

In: Scientific Reports, Vol. 7, 17091, 06.12.2017.

Research output: Contribution to journalArticle

Harvard

Tamburrino, G, Llabrés, S, Vickery, O, Pitt, SJ & Zachariae, U 2017, 'Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE', Scientific Reports, vol. 7, 17091. https://doi.org/10.1038/s41598-017-16995-x

APA

Tamburrino, G., Llabrés, S., Vickery, O., Pitt, S. J., & Zachariae, U. (2017). Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE. Scientific Reports, 7, [17091]. https://doi.org/10.1038/s41598-017-16995-x

Vancouver

Tamburrino G, Llabrés S, Vickery O, Pitt SJ, Zachariae U. Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE. Scientific Reports. 2017 Dec 6;7. 17091. https://doi.org/10.1038/s41598-017-16995-x

Author

Tamburrino, Giulia ; Llabrés, Salomé ; Vickery, Owen ; Pitt, Samantha Jane ; Zachariae, Ulrich. / Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE. In: Scientific Reports. 2017 ; Vol. 7.

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@article{b61ed622323d40c18aa22b77326a8c1d,
title = "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 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.",
author = "Giulia Tamburrino and Salom{\'e} Llabr{\'e}s and Owen Vickery and Pitt, {Samantha Jane} and Ulrich Zachariae",
note = "We acknowledge funding through the Wellcome Trust Interdisciplinary Research Funds (grant WT097818MF), the Scottish Universities’ Physics Alliance (SUPA), Tenovus Tayside (grant T16/30) and the Tayside Charitable Trust. O.N.V. has been funded through a BBSRC CASE award (BB/J013072/1).",
year = "2017",
month = "12",
day = "6",
doi = "10.1038/s41598-017-16995-x",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature publishing group",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE

AU - Tamburrino, Giulia

AU - Llabrés, Salomé

AU - Vickery, Owen

AU - Pitt, Samantha Jane

AU - Zachariae, Ulrich

N1 - We acknowledge funding through the Wellcome Trust Interdisciplinary Research Funds (grant WT097818MF), the Scottish Universities’ Physics Alliance (SUPA), Tenovus Tayside (grant T16/30) and the Tayside Charitable Trust. O.N.V. has been funded through a BBSRC CASE award (BB/J013072/1).

PY - 2017/12/6

Y1 - 2017/12/6

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-017-16995-x

DO - 10.1038/s41598-017-16995-x

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 17091

ER -

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