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Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus

The striking feature of the ubiquitous protein EfTu (Thermo unstable ribosomal Elongation factor) is its moonlighting (multifunctional) activity. Beyond its function at the ribosomal level it should be exported to the bacterial surface and act as an environmental sensor. In Bacillus cereus, and othe...

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Autores principales: N’Diaye, Awa R., Borrel, Valerie, Racine, Pierre-Jean, Clamens, Thomas, Depayras, Segolene, Maillot, Olivier, Schaack, Beatrice, Chevalier, Sylvie, Lesouhaitier, Olivier, Feuilloley, Marc G. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361937/
https://www.ncbi.nlm.nih.gov/pubmed/30718605
http://dx.doi.org/10.1038/s41598-018-37506-6
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author N’Diaye, Awa R.
Borrel, Valerie
Racine, Pierre-Jean
Clamens, Thomas
Depayras, Segolene
Maillot, Olivier
Schaack, Beatrice
Chevalier, Sylvie
Lesouhaitier, Olivier
Feuilloley, Marc G. J.
author_facet N’Diaye, Awa R.
Borrel, Valerie
Racine, Pierre-Jean
Clamens, Thomas
Depayras, Segolene
Maillot, Olivier
Schaack, Beatrice
Chevalier, Sylvie
Lesouhaitier, Olivier
Feuilloley, Marc G. J.
author_sort N’Diaye, Awa R.
collection PubMed
description The striking feature of the ubiquitous protein EfTu (Thermo unstable ribosomal Elongation factor) is its moonlighting (multifunctional) activity. Beyond its function at the ribosomal level it should be exported to the bacterial surface and act as an environmental sensor. In Bacillus cereus, and other cutaneous bacteria, it serves as a Substance P (SP) receptor and is essential for bacterial adaptation to the host. However, the modus operandi of EfTu as a bacterial sensor remains to be investigated. Studies realized by confocal and transmission electron microscopy revealed that, in the absence of an exogenous signal, EfTu is not exposed on the bacterial surface but is recruited under the effect of SP. In addition, SP acts as a transcriptional regulator of the tuf gene encoding for EfTu. As observed using gadolinium chloride, an inhibitor of membrane mechanosensitive channels (Msc), Msc control EfTu export and subsequently the bacterial response to SP both in terms of cytotoxicity and biofilm formation activity. Microscale thermophoresis revealed that in response to SP, EfTu can form homopolymers. This event should occur after EfTu export and, as shown by proteo-liposome reconstruction studies, SP appears to promote EfTu polymers association to the membrane, leading subsequently to the bacterial response. Molecular modeling suggests that this mechanism should involve EfTu unfolding and insertion into the bacterial cytoplasmic membrane, presumably through formation of homopolymers. This study is unraveling the original mechanism action of EfTu as a bacterial sensor but also reveals that this protein should have a broader role, including in eukaryotes.
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spelling pubmed-63619372019-02-06 Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus N’Diaye, Awa R. Borrel, Valerie Racine, Pierre-Jean Clamens, Thomas Depayras, Segolene Maillot, Olivier Schaack, Beatrice Chevalier, Sylvie Lesouhaitier, Olivier Feuilloley, Marc G. J. Sci Rep Article The striking feature of the ubiquitous protein EfTu (Thermo unstable ribosomal Elongation factor) is its moonlighting (multifunctional) activity. Beyond its function at the ribosomal level it should be exported to the bacterial surface and act as an environmental sensor. In Bacillus cereus, and other cutaneous bacteria, it serves as a Substance P (SP) receptor and is essential for bacterial adaptation to the host. However, the modus operandi of EfTu as a bacterial sensor remains to be investigated. Studies realized by confocal and transmission electron microscopy revealed that, in the absence of an exogenous signal, EfTu is not exposed on the bacterial surface but is recruited under the effect of SP. In addition, SP acts as a transcriptional regulator of the tuf gene encoding for EfTu. As observed using gadolinium chloride, an inhibitor of membrane mechanosensitive channels (Msc), Msc control EfTu export and subsequently the bacterial response to SP both in terms of cytotoxicity and biofilm formation activity. Microscale thermophoresis revealed that in response to SP, EfTu can form homopolymers. This event should occur after EfTu export and, as shown by proteo-liposome reconstruction studies, SP appears to promote EfTu polymers association to the membrane, leading subsequently to the bacterial response. Molecular modeling suggests that this mechanism should involve EfTu unfolding and insertion into the bacterial cytoplasmic membrane, presumably through formation of homopolymers. This study is unraveling the original mechanism action of EfTu as a bacterial sensor but also reveals that this protein should have a broader role, including in eukaryotes. Nature Publishing Group UK 2019-02-04 /pmc/articles/PMC6361937/ /pubmed/30718605 http://dx.doi.org/10.1038/s41598-018-37506-6 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
N’Diaye, Awa R.
Borrel, Valerie
Racine, Pierre-Jean
Clamens, Thomas
Depayras, Segolene
Maillot, Olivier
Schaack, Beatrice
Chevalier, Sylvie
Lesouhaitier, Olivier
Feuilloley, Marc G. J.
Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus
title Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus
title_full Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus
title_fullStr Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus
title_full_unstemmed Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus
title_short Mechanism of action of the moonlighting protein EfTu as a Substance P sensor in Bacillus cereus
title_sort mechanism of action of the moonlighting protein eftu as a substance p sensor in bacillus cereus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361937/
https://www.ncbi.nlm.nih.gov/pubmed/30718605
http://dx.doi.org/10.1038/s41598-018-37506-6
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