Cargando…

The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans

In most Streptomyces species, antibiotic production is triggered in a condition of phosphate limitation, a condition that is known to be correlated with a low intracellular ATP content compared to growth in a condition of phosphate proficiency. This observation suggests that a low ATP content might...

Descripción completa

Detalles Bibliográficos
Autores principales: Seghezzi, Nicolas, Darbon, Emmanuelle, Martel, Cécile, David, Michelle, Lejeune, Clara, Esnault, Catherine, Virolle, Marie-Joelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495134/
https://www.ncbi.nlm.nih.gov/pubmed/36139937
http://dx.doi.org/10.3390/antibiotics11091157
_version_ 1784793949469147136
author Seghezzi, Nicolas
Darbon, Emmanuelle
Martel, Cécile
David, Michelle
Lejeune, Clara
Esnault, Catherine
Virolle, Marie-Joelle
author_facet Seghezzi, Nicolas
Darbon, Emmanuelle
Martel, Cécile
David, Michelle
Lejeune, Clara
Esnault, Catherine
Virolle, Marie-Joelle
author_sort Seghezzi, Nicolas
collection PubMed
description In most Streptomyces species, antibiotic production is triggered in a condition of phosphate limitation, a condition that is known to be correlated with a low intracellular ATP content compared to growth in a condition of phosphate proficiency. This observation suggests that a low ATP content might be a direct trigger of antibiotic biosynthesis. In order to test this hypothesis, we introduced into the model strain Streptomyces lividans, a functional and a non-functional ATPase cloned into the replicative vector pOSV206 and expressed under the control of the strong ErmE* promoter. The functional ATPase was constituted by the α (AtpA), β (AtpB) and γ (AtpD) sub-units of the native F1 part of the ATP synthase of S. lividans that, when separated from the membrane-bound F0 part, bears an ATPase activity. The non-functional ATPase was a mutated version of the latter, bearing a 12 amino acids deletion encompassing the active site of the AtpD sub-unit. S. lividans was chosen to test our hypothesis since this strain hardly produces any antibiotics. However, it possesses the same biosynthetic pathways of various specialized metabolites as S. coelicolor, a phylogenetically closely related strain that produces these metabolites in abundance. Our results demonstrated that the over-expression of the functional ATPase, but not that of its mutated version, indeed correlated with the production of the bioactive metabolites of the CDA, RED and ACT clusters. These results confirmed the long known and mysterious link existing between a phosphate limitation leading to an ATP deficit and the triggering of antibiotic biosynthesis. Based on this work and the previous published results of our group, we propose an entirely novel conception of the nature of this link.
format Online
Article
Text
id pubmed-9495134
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94951342022-09-23 The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans Seghezzi, Nicolas Darbon, Emmanuelle Martel, Cécile David, Michelle Lejeune, Clara Esnault, Catherine Virolle, Marie-Joelle Antibiotics (Basel) Article In most Streptomyces species, antibiotic production is triggered in a condition of phosphate limitation, a condition that is known to be correlated with a low intracellular ATP content compared to growth in a condition of phosphate proficiency. This observation suggests that a low ATP content might be a direct trigger of antibiotic biosynthesis. In order to test this hypothesis, we introduced into the model strain Streptomyces lividans, a functional and a non-functional ATPase cloned into the replicative vector pOSV206 and expressed under the control of the strong ErmE* promoter. The functional ATPase was constituted by the α (AtpA), β (AtpB) and γ (AtpD) sub-units of the native F1 part of the ATP synthase of S. lividans that, when separated from the membrane-bound F0 part, bears an ATPase activity. The non-functional ATPase was a mutated version of the latter, bearing a 12 amino acids deletion encompassing the active site of the AtpD sub-unit. S. lividans was chosen to test our hypothesis since this strain hardly produces any antibiotics. However, it possesses the same biosynthetic pathways of various specialized metabolites as S. coelicolor, a phylogenetically closely related strain that produces these metabolites in abundance. Our results demonstrated that the over-expression of the functional ATPase, but not that of its mutated version, indeed correlated with the production of the bioactive metabolites of the CDA, RED and ACT clusters. These results confirmed the long known and mysterious link existing between a phosphate limitation leading to an ATP deficit and the triggering of antibiotic biosynthesis. Based on this work and the previous published results of our group, we propose an entirely novel conception of the nature of this link. MDPI 2022-08-27 /pmc/articles/PMC9495134/ /pubmed/36139937 http://dx.doi.org/10.3390/antibiotics11091157 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seghezzi, Nicolas
Darbon, Emmanuelle
Martel, Cécile
David, Michelle
Lejeune, Clara
Esnault, Catherine
Virolle, Marie-Joelle
The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans
title The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans
title_full The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans
title_fullStr The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans
title_full_unstemmed The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans
title_short The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans
title_sort generation of an artificial atp deficit triggers antibiotic production in streptomyces lividans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495134/
https://www.ncbi.nlm.nih.gov/pubmed/36139937
http://dx.doi.org/10.3390/antibiotics11091157
work_keys_str_mv AT seghezzinicolas thegenerationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT darbonemmanuelle thegenerationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT martelcecile thegenerationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT davidmichelle thegenerationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT lejeuneclara thegenerationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT esnaultcatherine thegenerationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT virollemariejoelle thegenerationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT seghezzinicolas generationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT darbonemmanuelle generationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT martelcecile generationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT davidmichelle generationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT lejeuneclara generationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT esnaultcatherine generationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans
AT virollemariejoelle generationofanartificialatpdeficittriggersantibioticproductioninstreptomyceslividans