Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery
Abstract Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about bacterial dormancy development and recovery. Previously, we established a corr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56387-8 |
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| _version_ | 1832585576288616448 |
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| author | Celien Bollen Sofie Louwagie Femke Deroover Wouter Duverger Ladan Khodaparast Laleh Khodaparast Dieter Hofkens Joost Schymkowitz Frederic Rousseau Liselot Dewachter Jan Michiels |
| author_facet | Celien Bollen Sofie Louwagie Femke Deroover Wouter Duverger Ladan Khodaparast Laleh Khodaparast Dieter Hofkens Joost Schymkowitz Frederic Rousseau Liselot Dewachter Jan Michiels |
| author_sort | Celien Bollen |
| collection | DOAJ |
| description | Abstract Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about bacterial dormancy development and recovery. Previously, we established a correlation between protein aggregation and dormancy in Escherichia coli. Here, we present further support for a direct relationship between both. Our experiments demonstrate that aggregates progressively sequester proteins involved in energy production, thereby likely causing ATP depletion and dormancy. Furthermore, we demonstrate that structural features of protein aggregates determine the cell’s ability to exit dormancy and resume growth. Proteins were shown to first assemble in liquid-like condensates that solidify over time. This liquid-to-solid phase transition impedes aggregate dissolution, thereby preventing growth resumption. Our data support a model in which aggregate structure, rather than cellular activity, marks the transition from the persister to the VBNC state. |
| format | Article |
| id | doaj-art-8252e88ff81846e88fd0577a2f874257 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8252e88ff81846e88fd0577a2f8742572025-01-26T12:40:48ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56387-8Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recoveryCelien Bollen0Sofie Louwagie1Femke Deroover2Wouter Duverger3Ladan Khodaparast4Laleh Khodaparast5Dieter Hofkens6Joost Schymkowitz7Frederic Rousseau8Liselot Dewachter9Jan Michiels10Centre of Microbial and Plant Genetics, KU LeuvenCentre of Microbial and Plant Genetics, KU LeuvenCentre of Microbial and Plant Genetics, KU LeuvenSwitch Laboratory, Center for Brain and Disease Research, VIB-KU LeuvenSwitch Laboratory, Center for Brain and Disease Research, VIB-KU LeuvenSwitch Laboratory, Center for Brain and Disease Research, VIB-KU LeuvenCentre of Microbial and Plant Genetics, KU LeuvenSwitch Laboratory, Center for Brain and Disease Research, VIB-KU LeuvenSwitch Laboratory, Center for Brain and Disease Research, VIB-KU LeuvenCentre of Microbial and Plant Genetics, KU LeuvenCentre of Microbial and Plant Genetics, KU LeuvenAbstract Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about bacterial dormancy development and recovery. Previously, we established a correlation between protein aggregation and dormancy in Escherichia coli. Here, we present further support for a direct relationship between both. Our experiments demonstrate that aggregates progressively sequester proteins involved in energy production, thereby likely causing ATP depletion and dormancy. Furthermore, we demonstrate that structural features of protein aggregates determine the cell’s ability to exit dormancy and resume growth. Proteins were shown to first assemble in liquid-like condensates that solidify over time. This liquid-to-solid phase transition impedes aggregate dissolution, thereby preventing growth resumption. Our data support a model in which aggregate structure, rather than cellular activity, marks the transition from the persister to the VBNC state.https://doi.org/10.1038/s41467-025-56387-8 |
| spellingShingle | Celien Bollen Sofie Louwagie Femke Deroover Wouter Duverger Ladan Khodaparast Laleh Khodaparast Dieter Hofkens Joost Schymkowitz Frederic Rousseau Liselot Dewachter Jan Michiels Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery Nature Communications |
| title | Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery |
| title_full | Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery |
| title_fullStr | Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery |
| title_full_unstemmed | Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery |
| title_short | Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery |
| title_sort | composition and liquid to solid maturation of protein aggregates contribute to bacterial dormancy development and recovery |
| url | https://doi.org/10.1038/s41467-025-56387-8 |
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