Oxygen concentration modulates colibactin production
ABSTRACTUp to 25% of the E. coli strains isolated from the feces of healthy humans harbor the pks genomic island encoding the synthesis of colibactin, a genotoxic metabolite. Evidence is accumulating for an etiologic role of colibactin in colorectal cancer. Little is known about the conditions of ex...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2023.2222437 |
| _version_ | 1797236672336756736 |
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| author | Nadège Bossuet Cécile Guyonnet Camille V Chagneau Min Tang-Fichaux Marie Penary Dorian Loubet Priscilla Branchu Eric Oswald Jean-Philippe Nougayrede |
| author_facet | Nadège Bossuet Cécile Guyonnet Camille V Chagneau Min Tang-Fichaux Marie Penary Dorian Loubet Priscilla Branchu Eric Oswald Jean-Philippe Nougayrede |
| author_sort | Nadège Bossuet |
| collection | DOAJ |
| description | ABSTRACTUp to 25% of the E. coli strains isolated from the feces of healthy humans harbor the pks genomic island encoding the synthesis of colibactin, a genotoxic metabolite. Evidence is accumulating for an etiologic role of colibactin in colorectal cancer. Little is known about the conditions of expression of colibactin in the gut. The intestine is characterized by a unique oxygenation profile, with a steep gradient between the physiological hypoxic epithelial surface and the anaerobic lumen, which favors the dominance of obligate anaerobes. Here, we report that colibactin production is maximal under anoxic conditions and decreases with increased oxygen concentration. We show that the aerobic respiration control (ArcA) positively regulates colibactin production and genotoxicity of pks+ E. coli in response to oxygen availability. Thus, colibactin synthesis is inhibited by oxygen, indicating that the pks biosynthetic pathway is adapted to the anoxic intestinal lumen and to the hypoxic infected or tumor tissue. |
| first_indexed | 2024-03-11T14:20:37Z |
| format | Article |
| id | doaj.art-a7e887f726c34b09864f17adf07da9be |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-24T17:07:34Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-a7e887f726c34b09864f17adf07da9be2024-03-28T22:38:19ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115110.1080/19490976.2023.2222437Oxygen concentration modulates colibactin productionNadège Bossuet0Cécile Guyonnet1Camille V Chagneau2Min Tang-Fichaux3Marie Penary4Dorian Loubet5Priscilla Branchu6Eric Oswald7Jean-Philippe Nougayrede8IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceIRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, FranceABSTRACTUp to 25% of the E. coli strains isolated from the feces of healthy humans harbor the pks genomic island encoding the synthesis of colibactin, a genotoxic metabolite. Evidence is accumulating for an etiologic role of colibactin in colorectal cancer. Little is known about the conditions of expression of colibactin in the gut. The intestine is characterized by a unique oxygenation profile, with a steep gradient between the physiological hypoxic epithelial surface and the anaerobic lumen, which favors the dominance of obligate anaerobes. Here, we report that colibactin production is maximal under anoxic conditions and decreases with increased oxygen concentration. We show that the aerobic respiration control (ArcA) positively regulates colibactin production and genotoxicity of pks+ E. coli in response to oxygen availability. Thus, colibactin synthesis is inhibited by oxygen, indicating that the pks biosynthetic pathway is adapted to the anoxic intestinal lumen and to the hypoxic infected or tumor tissue.https://www.tandfonline.com/doi/10.1080/19490976.2023.2222437Escherichia colicolibactinDNA damageoxygenhypoxia |
| spellingShingle | Nadège Bossuet Cécile Guyonnet Camille V Chagneau Min Tang-Fichaux Marie Penary Dorian Loubet Priscilla Branchu Eric Oswald Jean-Philippe Nougayrede Oxygen concentration modulates colibactin production Gut Microbes Escherichia coli colibactin DNA damage oxygen hypoxia |
| title | Oxygen concentration modulates colibactin production |
| title_full | Oxygen concentration modulates colibactin production |
| title_fullStr | Oxygen concentration modulates colibactin production |
| title_full_unstemmed | Oxygen concentration modulates colibactin production |
| title_short | Oxygen concentration modulates colibactin production |
| title_sort | oxygen concentration modulates colibactin production |
| topic | Escherichia coli colibactin DNA damage oxygen hypoxia |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2023.2222437 |
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