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The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages

Efflux pumps are membrane protein complexes conserved in all living organisms. Beyond being involved in antibiotic extrusion in several bacteria, efflux pumps are emerging as relevant players in pathogen-host interactions. We have investigated on the possible role of the efflux pump network in Shige...

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Autores principales: Pasqua, Martina, Grossi, Milena, Scinicariello, Sara, Aussel, Laurent, Barras, Frédéric, Colonna, Bianca, Prosseda, Gianni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393483/
https://www.ncbi.nlm.nih.gov/pubmed/30814604
http://dx.doi.org/10.1038/s41598-019-39749-3
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author Pasqua, Martina
Grossi, Milena
Scinicariello, Sara
Aussel, Laurent
Barras, Frédéric
Colonna, Bianca
Prosseda, Gianni
author_facet Pasqua, Martina
Grossi, Milena
Scinicariello, Sara
Aussel, Laurent
Barras, Frédéric
Colonna, Bianca
Prosseda, Gianni
author_sort Pasqua, Martina
collection PubMed
description Efflux pumps are membrane protein complexes conserved in all living organisms. Beyond being involved in antibiotic extrusion in several bacteria, efflux pumps are emerging as relevant players in pathogen-host interactions. We have investigated on the possible role of the efflux pump network in Shigella flexneri, the etiological agent of bacillary dysentery. We have found that S. flexneri has retained 14 of the 20 pumps characterized in Escherichia coli and that their expression is differentially modulated during the intracellular life of Shigella. In particular, the emrKY operon, encoding an efflux pump of the Major Facilitator Superfamily, is specifically and highly induced in Shigella-infected U937 macrophage-like cells and is activated in response to a combination of high K(+) and acidic pH, which are sensed by the EvgS/EvgA two-component system. Notably, we show that following S. flexneri infection, macrophage cytosol undergoes a mild reduction of intracellular pH, permitting EvgA to trigger the emrKY activation. Finally, we present data suggesting that EmrKY is required for the survival of Shigella in the harsh macrophage environment, highlighting for the first time the key role of an efflux pump during the Shigella invasive process.
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spelling pubmed-63934832019-03-01 The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages Pasqua, Martina Grossi, Milena Scinicariello, Sara Aussel, Laurent Barras, Frédéric Colonna, Bianca Prosseda, Gianni Sci Rep Article Efflux pumps are membrane protein complexes conserved in all living organisms. Beyond being involved in antibiotic extrusion in several bacteria, efflux pumps are emerging as relevant players in pathogen-host interactions. We have investigated on the possible role of the efflux pump network in Shigella flexneri, the etiological agent of bacillary dysentery. We have found that S. flexneri has retained 14 of the 20 pumps characterized in Escherichia coli and that their expression is differentially modulated during the intracellular life of Shigella. In particular, the emrKY operon, encoding an efflux pump of the Major Facilitator Superfamily, is specifically and highly induced in Shigella-infected U937 macrophage-like cells and is activated in response to a combination of high K(+) and acidic pH, which are sensed by the EvgS/EvgA two-component system. Notably, we show that following S. flexneri infection, macrophage cytosol undergoes a mild reduction of intracellular pH, permitting EvgA to trigger the emrKY activation. Finally, we present data suggesting that EmrKY is required for the survival of Shigella in the harsh macrophage environment, highlighting for the first time the key role of an efflux pump during the Shigella invasive process. Nature Publishing Group UK 2019-02-27 /pmc/articles/PMC6393483/ /pubmed/30814604 http://dx.doi.org/10.1038/s41598-019-39749-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pasqua, Martina
Grossi, Milena
Scinicariello, Sara
Aussel, Laurent
Barras, Frédéric
Colonna, Bianca
Prosseda, Gianni
The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages
title The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages
title_full The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages
title_fullStr The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages
title_full_unstemmed The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages
title_short The MFS efflux pump EmrKY contributes to the survival of Shigella within macrophages
title_sort mfs efflux pump emrky contributes to the survival of shigella within macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393483/
https://www.ncbi.nlm.nih.gov/pubmed/30814604
http://dx.doi.org/10.1038/s41598-019-39749-3
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