Colibactin-induced damage in bacteria is cell contact independent
ABSTRACT The bacterial toxin colibactin, produced primarily by the B2 phylogroup of Escherichia coli, underlies some cases of colorectal cancers. Colibactin crosslinks DNA and induces genotoxic damage in both mammalian and bacterial cells. While the mechanisms facilitating colibactin delivery remain...
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American Society for Microbiology
2025-01-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01875-24 |
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| author | Emily Lowry Amir Mitchell |
| author_facet | Emily Lowry Amir Mitchell |
| author_sort | Emily Lowry |
| collection | DOAJ |
| description | ABSTRACT The bacterial toxin colibactin, produced primarily by the B2 phylogroup of Escherichia coli, underlies some cases of colorectal cancers. Colibactin crosslinks DNA and induces genotoxic damage in both mammalian and bacterial cells. While the mechanisms facilitating colibactin delivery remain unclear, results from multiple studies supported a delivery model that necessitates cell-cell contact. We directly tested this requirement in bacterial cultures by monitoring the spatiotemporal dynamics of the DNA damage response using a fluorescent transcriptional reporter. We found that in mixed-cell populations, DNA damage saturated within 12 hours and was detectable even in reporter cells separated from colibactin producers by hundreds of microns. Experiments with distinctly separated producer and reporter colonies revealed that the intensity of DNA damage decays similarly with distance regardless of colony contact. Our work reveals that cell contact is inconsequential for colibactin delivery in bacteria and suggests that contact dependence needs to be reexamined in mammalian cells as well.IMPORTANCEColibactin is a bacteria-produced toxin that binds and damages DNA. It has been widely studied in mammalian cells due to its potential role in tumorigenesis. However, fundamental questions about its impact in bacteria remain underexplored. We used Escherichia coli as a model system to study colibactin toxicity in neighboring bacteria and directly tested if cell-cell contact is required for toxicity, as has previously been proposed. We found that colibactin can induce DNA damage in bacteria hundreds of microns away, and the intensity of DNA damage presents similarly regardless of cell-cell contact. Our work further suggests that the requirement for cell-cell contact for colibactin-induced toxicity also needs to be reevaluated in mammalian cells. |
| format | Article |
| id | doaj-art-ad9473016a694be182461a4e1aed95ac |
| institution | Kabale University |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Society for Microbiology |
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| series | mBio |
| spelling | doaj-art-ad9473016a694be182461a4e1aed95ac2025-01-08T14:00:38ZengAmerican Society for MicrobiologymBio2150-75112025-01-0116110.1128/mbio.01875-24Colibactin-induced damage in bacteria is cell contact independentEmily Lowry0Amir Mitchell1Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USADepartment of Systems Biology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USAABSTRACT The bacterial toxin colibactin, produced primarily by the B2 phylogroup of Escherichia coli, underlies some cases of colorectal cancers. Colibactin crosslinks DNA and induces genotoxic damage in both mammalian and bacterial cells. While the mechanisms facilitating colibactin delivery remain unclear, results from multiple studies supported a delivery model that necessitates cell-cell contact. We directly tested this requirement in bacterial cultures by monitoring the spatiotemporal dynamics of the DNA damage response using a fluorescent transcriptional reporter. We found that in mixed-cell populations, DNA damage saturated within 12 hours and was detectable even in reporter cells separated from colibactin producers by hundreds of microns. Experiments with distinctly separated producer and reporter colonies revealed that the intensity of DNA damage decays similarly with distance regardless of colony contact. Our work reveals that cell contact is inconsequential for colibactin delivery in bacteria and suggests that contact dependence needs to be reexamined in mammalian cells as well.IMPORTANCEColibactin is a bacteria-produced toxin that binds and damages DNA. It has been widely studied in mammalian cells due to its potential role in tumorigenesis. However, fundamental questions about its impact in bacteria remain underexplored. We used Escherichia coli as a model system to study colibactin toxicity in neighboring bacteria and directly tested if cell-cell contact is required for toxicity, as has previously been proposed. We found that colibactin can induce DNA damage in bacteria hundreds of microns away, and the intensity of DNA damage presents similarly regardless of cell-cell contact. Our work further suggests that the requirement for cell-cell contact for colibactin-induced toxicity also needs to be reevaluated in mammalian cells.https://journals.asm.org/doi/10.1128/mbio.01875-24colibactintoxinsDNA damagefluorescent image analysis |
| spellingShingle | Emily Lowry Amir Mitchell Colibactin-induced damage in bacteria is cell contact independent mBio colibactin toxins DNA damage fluorescent image analysis |
| title | Colibactin-induced damage in bacteria is cell contact independent |
| title_full | Colibactin-induced damage in bacteria is cell contact independent |
| title_fullStr | Colibactin-induced damage in bacteria is cell contact independent |
| title_full_unstemmed | Colibactin-induced damage in bacteria is cell contact independent |
| title_short | Colibactin-induced damage in bacteria is cell contact independent |
| title_sort | colibactin induced damage in bacteria is cell contact independent |
| topic | colibactin toxins DNA damage fluorescent image analysis |
| url | https://journals.asm.org/doi/10.1128/mbio.01875-24 |
| work_keys_str_mv | AT emilylowry colibactininduceddamageinbacteriaiscellcontactindependent AT amirmitchell colibactininduceddamageinbacteriaiscellcontactindependent |