Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality
<jats:title>Abstract</jats:title><jats:p>Bactericidal antibiotics kill bacteria by perturbing various cellular targets and processes. Disruption of the primary antibiotic-binding partner induces a cascade of molecular events, leading to overproduction of reactive metabolic by-produ...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/136155 |
| _version_ | 1826215601724456960 |
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| author | Wong, Felix Stokes, Jonathan M Cervantes, Bernardo Penkov, Sider Friedrichs, Jens Renner, Lars D Collins, James J |
| author_facet | Wong, Felix Stokes, Jonathan M Cervantes, Bernardo Penkov, Sider Friedrichs, Jens Renner, Lars D Collins, James J |
| author_sort | Wong, Felix |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Bactericidal antibiotics kill bacteria by perturbing various cellular targets and processes. Disruption of the primary antibiotic-binding partner induces a cascade of molecular events, leading to overproduction of reactive metabolic by-products. It remains unclear, however, how these molecular events contribute to bacterial cell death. Here, we take a single-cell physical biology approach to probe antibiotic function. We show that aminoglycosides and fluoroquinolones induce cytoplasmic condensation through membrane damage and subsequent outflow of cytoplasmic contents as part of their lethality. A quantitative model of membrane damage and cytoplasmic leakage indicates that a small number of nanometer-scale membrane defects in a single bacterium can give rise to the cellular-scale phenotype of cytoplasmic condensation. Furthermore, cytoplasmic condensation is associated with the accumulation of reactive metabolic by-products and lipid peroxidation, and pretreatment of cells with the antioxidant glutathione attenuates cytoplasmic condensation and cell death. Our work expands our understanding of the downstream molecular events that are associated with antibiotic lethality, revealing cytoplasmic condensation as a phenotypic feature of antibiotic-induced bacterial cell death.</jats:p> |
| first_indexed | 2024-09-23T16:36:30Z |
| format | Article |
| id | mit-1721.1/136155 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:36:30Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1361552021-10-28T03:09:07Z Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality Wong, Felix Stokes, Jonathan M Cervantes, Bernardo Penkov, Sider Friedrichs, Jens Renner, Lars D Collins, James J <jats:title>Abstract</jats:title><jats:p>Bactericidal antibiotics kill bacteria by perturbing various cellular targets and processes. Disruption of the primary antibiotic-binding partner induces a cascade of molecular events, leading to overproduction of reactive metabolic by-products. It remains unclear, however, how these molecular events contribute to bacterial cell death. Here, we take a single-cell physical biology approach to probe antibiotic function. We show that aminoglycosides and fluoroquinolones induce cytoplasmic condensation through membrane damage and subsequent outflow of cytoplasmic contents as part of their lethality. A quantitative model of membrane damage and cytoplasmic leakage indicates that a small number of nanometer-scale membrane defects in a single bacterium can give rise to the cellular-scale phenotype of cytoplasmic condensation. Furthermore, cytoplasmic condensation is associated with the accumulation of reactive metabolic by-products and lipid peroxidation, and pretreatment of cells with the antioxidant glutathione attenuates cytoplasmic condensation and cell death. Our work expands our understanding of the downstream molecular events that are associated with antibiotic lethality, revealing cytoplasmic condensation as a phenotypic feature of antibiotic-induced bacterial cell death.</jats:p> 2021-10-27T20:31:08Z 2021-10-27T20:31:08Z 2021-12 2021-08-25T17:53:07Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136155 en 10.1038/s41467-021-22485-6 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Wong, Felix Stokes, Jonathan M Cervantes, Bernardo Penkov, Sider Friedrichs, Jens Renner, Lars D Collins, James J Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality |
| title | Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality |
| title_full | Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality |
| title_fullStr | Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality |
| title_full_unstemmed | Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality |
| title_short | Cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality |
| title_sort | cytoplasmic condensation induced by membrane damage is associated with antibiotic lethality |
| url | https://hdl.handle.net/1721.1/136155 |
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