Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes
Levofloxacin is a broad-spectrum fluoroquinolone antibiotic in clinical use that targets DNA gyrase in the cytosol. It is used in systemic applications via oral or intravenous route, and its pharmacokinetics and access to its molecular targets are strongly influenced by interactions with cellular me...
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| مؤلفون آخرون: | , , , , |
| منشور في: |
2025
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| _version_ | 1852014294958342144 |
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| author | D. Ralph (19979967) |
| author2 | A. Goode (22767051) V. Yeh (22767054) J. M. A. Blair (22767057) P. Williams (1634566) B. B. Bonev (22767060) |
| author2_role | author author author author author |
| author_facet | D. Ralph (19979967) A. Goode (22767051) V. Yeh (22767054) J. M. A. Blair (22767057) P. Williams (1634566) B. B. Bonev (22767060) |
| author_role | author |
| dc.creator.none.fl_str_mv | D. Ralph (19979967) A. Goode (22767051) V. Yeh (22767054) J. M. A. Blair (22767057) P. Williams (1634566) B. B. Bonev (22767060) |
| dc.date.none.fl_str_mv | 2025-12-03T09:11:46Z |
| dc.identifier.none.fl_str_mv | 10.1021/acs.langmuir.5c04836.s002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/media/Molecular_Interactions_of_Fluoroquinolone_Antibiotics_with_Lipid_Membranes/30773422 |
| dc.rights.none.fl_str_mv | CC BY-NC 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biophysics Biochemistry Medicine Biotechnology Virology Computational Biology Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified using zwitterionic dopc negatively charged dopc negatively charged bilayers targets dna gyrase monomeric soluble population spectrum fluoroquinolone antibiotic molecular population embedded fractional membrane insertion dopg lipid membranes associated molecular assemblies lipid membranes levofloxacin fast exchange equilibrium molecular targets lipid membranes associated population solvated population lipid bilayer fluoroquinolone antibiotics cellular membranes antibiotic concentration strongly influenced solubility limits solubility limit physical state observe concentration negative lipids molecular interactions membrane charge md simulations levofloxacin solutions intravenous route clinical use |
| dc.title.none.fl_str_mv | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes |
| dc.type.none.fl_str_mv | Dataset Media info:eu-repo/semantics/publishedVersion dataset |
| description | Levofloxacin is a broad-spectrum fluoroquinolone antibiotic in clinical use that targets DNA gyrase in the cytosol. It is used in systemic applications via oral or intravenous route, and its pharmacokinetics and access to its molecular targets are strongly influenced by interactions with cellular membranes. We used NMR and MD simulations to investigate the physical state of levofloxacin in solution and its interactions with lipid membranes, assessing the role of membrane charge and antibiotic concentration. Using zwitterionic DOPC and negatively charged DOPC/DOPG lipid membranes, we observe concentration-dependent self-association of levofloxacin in solution below its solubility limits and association with lipid membranes with a preference for negatively charged bilayers. Below the solubility limit, levofloxacin solutions that appear clear contain self-associated molecular assemblies in fast exchange equilibrium with a monomeric soluble population. In the presence of lipid membranes, this equilibrium is shifted in favor of a membrane-associated population with preference for negative lipids. MD simulations show levofloxacin condensation in solution and fractional membrane insertion, which suggest the presence of a molecular population embedded in the lipid bilayer, coexisting with self-associated levofloxacin molecular “droplets” in exchange with a solvated population. |
| eu_rights_str_mv | openAccess |
| id | Manara_6f63d7300a236aacfdee26da196d4db7 |
| identifier_str_mv | 10.1021/acs.langmuir.5c04836.s002 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30773422 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY-NC 4.0 |
| spelling | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid MembranesD. Ralph (19979967)A. Goode (22767051)V. Yeh (22767054)J. M. A. Blair (22767057)P. Williams (1634566)B. B. Bonev (22767060)BiophysicsBiochemistryMedicineBiotechnologyVirologyComputational BiologyChemical Sciences not elsewhere classifiedPhysical Sciences not elsewhere classifiedusing zwitterionic dopcnegatively charged dopcnegatively charged bilayerstargets dna gyrasemonomeric soluble populationspectrum fluoroquinolone antibioticmolecular population embeddedfractional membrane insertiondopg lipid membranesassociated molecular assemblieslipid membranes levofloxacinfast exchange equilibriummolecular targetslipid membranesassociated populationsolvated populationlipid bilayerfluoroquinolone antibioticscellular membranesantibiotic concentrationstrongly influencedsolubility limitssolubility limitphysical stateobserve concentrationnegative lipidsmolecular interactionsmembrane chargemd simulationslevofloxacin solutionsintravenous routeclinical useLevofloxacin is a broad-spectrum fluoroquinolone antibiotic in clinical use that targets DNA gyrase in the cytosol. It is used in systemic applications via oral or intravenous route, and its pharmacokinetics and access to its molecular targets are strongly influenced by interactions with cellular membranes. We used NMR and MD simulations to investigate the physical state of levofloxacin in solution and its interactions with lipid membranes, assessing the role of membrane charge and antibiotic concentration. Using zwitterionic DOPC and negatively charged DOPC/DOPG lipid membranes, we observe concentration-dependent self-association of levofloxacin in solution below its solubility limits and association with lipid membranes with a preference for negatively charged bilayers. Below the solubility limit, levofloxacin solutions that appear clear contain self-associated molecular assemblies in fast exchange equilibrium with a monomeric soluble population. In the presence of lipid membranes, this equilibrium is shifted in favor of a membrane-associated population with preference for negative lipids. MD simulations show levofloxacin condensation in solution and fractional membrane insertion, which suggest the presence of a molecular population embedded in the lipid bilayer, coexisting with self-associated levofloxacin molecular “droplets” in exchange with a solvated population.2025-12-03T09:11:46ZDatasetMediainfo:eu-repo/semantics/publishedVersiondataset10.1021/acs.langmuir.5c04836.s002https://figshare.com/articles/media/Molecular_Interactions_of_Fluoroquinolone_Antibiotics_with_Lipid_Membranes/30773422CC BY-NC 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307734222025-12-03T09:11:46Z |
| spellingShingle | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes D. Ralph (19979967) Biophysics Biochemistry Medicine Biotechnology Virology Computational Biology Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified using zwitterionic dopc negatively charged dopc negatively charged bilayers targets dna gyrase monomeric soluble population spectrum fluoroquinolone antibiotic molecular population embedded fractional membrane insertion dopg lipid membranes associated molecular assemblies lipid membranes levofloxacin fast exchange equilibrium molecular targets lipid membranes associated population solvated population lipid bilayer fluoroquinolone antibiotics cellular membranes antibiotic concentration strongly influenced solubility limits solubility limit physical state observe concentration negative lipids molecular interactions membrane charge md simulations levofloxacin solutions intravenous route clinical use |
| status_str | publishedVersion |
| title | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes |
| title_full | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes |
| title_fullStr | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes |
| title_full_unstemmed | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes |
| title_short | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes |
| title_sort | Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes |
| topic | Biophysics Biochemistry Medicine Biotechnology Virology Computational Biology Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified using zwitterionic dopc negatively charged dopc negatively charged bilayers targets dna gyrase monomeric soluble population spectrum fluoroquinolone antibiotic molecular population embedded fractional membrane insertion dopg lipid membranes associated molecular assemblies lipid membranes levofloxacin fast exchange equilibrium molecular targets lipid membranes associated population solvated population lipid bilayer fluoroquinolone antibiotics cellular membranes antibiotic concentration strongly influenced solubility limits solubility limit physical state observe concentration negative lipids molecular interactions membrane charge md simulations levofloxacin solutions intravenous route clinical use |