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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Giulia Tamburrino, Salomé Llabrés, Owen N. Vickery, Samantha J. Pitt, Ulrich Zachariae
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/14bb12e59497474ea99ab84771bb053c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:14bb12e59497474ea99ab84771bb053c
record_format	dspace
spelling	oai:doaj.org-article:14bb12e59497474ea99ab84771bb053c2021-12-02T15:05:24ZModulation of the Neisseria gonorrhoeae drug efflux conduit MtrE10.1038/s41598-017-16995-x2045-2322https://doaj.org/article/14bb12e59497474ea99ab84771bb053c2017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16995-xhttps://doaj.org/toc/2045-2322Abstract 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.Giulia TamburrinoSalomé LlabrésOwen N. VickerySamantha J. PittUlrich ZachariaeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giulia Tamburrino Salomé Llabrés Owen N. Vickery Samantha J. Pitt Ulrich Zachariae Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE
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.
format	article
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
title	Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE
title_short	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_sort	modulation of the neisseria gonorrhoeae drug efflux conduit mtre
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/14bb12e59497474ea99ab84771bb053c
work_keys_str_mv	AT giuliatamburrino modulationoftheneisseriagonorrhoeaedrugeffluxconduitmtre AT salomellabres modulationoftheneisseriagonorrhoeaedrugeffluxconduitmtre AT owennvickery modulationoftheneisseriagonorrhoeaedrugeffluxconduitmtre AT samanthajpitt modulationoftheneisseriagonorrhoeaedrugeffluxconduitmtre AT ulrichzachariae modulationoftheneisseriagonorrhoeaedrugeffluxconduitmtre
_version_	1718388814445019136

Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE

Ejemplares similares