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- Publisher Website: 10.1126/science.aat9689
- Scopus: eid_2-s2.0-85068677736
- PMID: 31249058
- WOS: WOS:000473271300047
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Article: Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages
Title | Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages |
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Authors | |
Issue Date | 2019 |
Citation | Science, 2019, v. 364, n. 6447, p. 1279-1282 How to Cite? |
Abstract | Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, remains the world's deadliest infectious disease. Sterilizing chemotherapy requires at least 6 months of multidrug therapy. Difficulty visualizing the subcellular localization of antibiotics in infected host cells means that it is unclear whether antibiotics penetrate all mycobacteria-containing compartments in the cell. Here, we combined correlated light, electron, and ion microscopy to image the distribution of bedaquiline in infected human macrophages at submicrometer resolution. Bedaquiline accumulated primarily in host cell lipid droplets, but heterogeneously in mycobacteria within a variety of intracellular compartments. Furthermore, lipid droplets did not sequester antibiotic but constituted a transferable reservoir that enhanced antibacterial efficacy. Thus, strong lipid binding facilitated drug trafficking by host organelles to an intracellular target during antimicrobial treatment. |
Persistent Identifier | http://hdl.handle.net/10722/301841 |
ISSN | 2023 Impact Factor: 44.7 2023 SCImago Journal Rankings: 11.902 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Greenwood, Daniel J. | - |
dc.contributor.author | Dos Santos, Mariana Silva | - |
dc.contributor.author | Huang, Song | - |
dc.contributor.author | Russell, Matthew R.G. | - |
dc.contributor.author | Collinson, Lucy M. | - |
dc.contributor.author | MacRae, James I. | - |
dc.contributor.author | West, Andy | - |
dc.contributor.author | Jiang, Haibo | - |
dc.contributor.author | Gutierrez, Maximiliano G. | - |
dc.date.accessioned | 2021-08-19T02:20:51Z | - |
dc.date.available | 2021-08-19T02:20:51Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Science, 2019, v. 364, n. 6447, p. 1279-1282 | - |
dc.identifier.issn | 0036-8075 | - |
dc.identifier.uri | http://hdl.handle.net/10722/301841 | - |
dc.description.abstract | Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, remains the world's deadliest infectious disease. Sterilizing chemotherapy requires at least 6 months of multidrug therapy. Difficulty visualizing the subcellular localization of antibiotics in infected host cells means that it is unclear whether antibiotics penetrate all mycobacteria-containing compartments in the cell. Here, we combined correlated light, electron, and ion microscopy to image the distribution of bedaquiline in infected human macrophages at submicrometer resolution. Bedaquiline accumulated primarily in host cell lipid droplets, but heterogeneously in mycobacteria within a variety of intracellular compartments. Furthermore, lipid droplets did not sequester antibiotic but constituted a transferable reservoir that enhanced antibacterial efficacy. Thus, strong lipid binding facilitated drug trafficking by host organelles to an intracellular target during antimicrobial treatment. | - |
dc.language | eng | - |
dc.relation.ispartof | Science | - |
dc.title | Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1126/science.aat9689 | - |
dc.identifier.pmid | 31249058 | - |
dc.identifier.pmcid | PMC7012645 | - |
dc.identifier.scopus | eid_2-s2.0-85068677736 | - |
dc.identifier.volume | 364 | - |
dc.identifier.issue | 6447 | - |
dc.identifier.spage | 1279 | - |
dc.identifier.epage | 1282 | - |
dc.identifier.eissn | 1095-9203 | - |
dc.identifier.isi | WOS:000473271300047 | - |