The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i>
In most <i>Streptomyces</i> 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/9/1157 |
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| author | Nicolas Seghezzi Emmanuelle Darbon Cécile Martel Michelle David Clara Lejeune Catherine Esnault Marie-Joelle Virolle |
| author_facet | Nicolas Seghezzi Emmanuelle Darbon Cécile Martel Michelle David Clara Lejeune Catherine Esnault Marie-Joelle Virolle |
| author_sort | Nicolas Seghezzi |
| collection | DOAJ |
| description | In most <i>Streptomyces</i> 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 <i>Streptomyces lividans</i>, 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 <i>S. lividans</i> 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. <i>S. lividans</i> 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 <i>S. coelicolor</i>, 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. |
| first_indexed | 2024-03-10T00:56:15Z |
| format | Article |
| id | doaj.art-ecb9bac3b46c495c81cc2b0b672effed |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T00:56:15Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-ecb9bac3b46c495c81cc2b0b672effed2023-11-23T14:43:58ZengMDPI AGAntibiotics2079-63822022-08-01119115710.3390/antibiotics11091157The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i>Nicolas Seghezzi0Emmanuelle Darbon1Cécile Martel2Michelle David3Clara Lejeune4Catherine Esnault5Marie-Joelle Virolle6Institute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceInstitute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceInstitute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceInstitute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceInstitute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceInstitute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceInstitute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS, 91198 Gif-sur-Yvette, FranceIn most <i>Streptomyces</i> 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 <i>Streptomyces lividans</i>, 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 <i>S. lividans</i> 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. <i>S. lividans</i> 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 <i>S. coelicolor</i>, 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.https://www.mdpi.com/2079-6382/11/9/1157phosphate limitationATP deficitoxidative phosphorylationoxidative stressATPaseantibiotics |
| spellingShingle | Nicolas Seghezzi Emmanuelle Darbon Cécile Martel Michelle David Clara Lejeune Catherine Esnault Marie-Joelle Virolle The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i> Antibiotics phosphate limitation ATP deficit oxidative phosphorylation oxidative stress ATPase antibiotics |
| title | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i> |
| title_full | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i> |
| title_fullStr | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i> |
| title_full_unstemmed | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i> |
| title_short | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in <i>Streptomyces lividans</i> |
| title_sort | generation of an artificial atp deficit triggers antibiotic production in i streptomyces lividans i |
| topic | phosphate limitation ATP deficit oxidative phosphorylation oxidative stress ATPase antibiotics |
| url | https://www.mdpi.com/2079-6382/11/9/1157 |
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