Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs

Correlative light, electron, and ion microscopy (CLEIM) offers huge potential to track the intracellular fate of antibiotics, with organelle-level resolution. However, a correlative approach that enables subcellular antibiotic visualisation in pathogen-infected tissue is lacking. Here, we developed...

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Autores principales: Fearns, Antony, Greenwood, Daniel J., Rodgers, Angela, Jiang, Haibo, Gutierrez, Maximiliano G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Methods and Resources
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810513/
https://www.ncbi.nlm.nih.gov/pubmed/33382684
http://dx.doi.org/10.1371/journal.pbio.3000879
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author Fearns, Antony
Greenwood, Daniel J.
Rodgers, Angela
Jiang, Haibo
Gutierrez, Maximiliano G.
author_facet Fearns, Antony
Greenwood, Daniel J.
Rodgers, Angela
Jiang, Haibo
Gutierrez, Maximiliano G.
author_sort Fearns, Antony
collection PubMed
description Correlative light, electron, and ion microscopy (CLEIM) offers huge potential to track the intracellular fate of antibiotics, with organelle-level resolution. However, a correlative approach that enables subcellular antibiotic visualisation in pathogen-infected tissue is lacking. Here, we developed correlative light, electron, and ion microscopy in tissue (CLEIMiT) and used it to identify the cell type–specific accumulation of an antibiotic in lung lesions of mice infected with Mycobacterium tuberculosis. Using CLEIMiT, we found that the anti-tuberculosis (TB) drug bedaquiline (BDQ) is localised not only in foamy macrophages in the lungs during infection but also accumulate in polymorphonuclear (PMN) cells.
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spelling pubmed-78105132021-01-27 Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs Fearns, Antony Greenwood, Daniel J. Rodgers, Angela Jiang, Haibo Gutierrez, Maximiliano G. PLoS Biol Methods and Resources Correlative light, electron, and ion microscopy (CLEIM) offers huge potential to track the intracellular fate of antibiotics, with organelle-level resolution. However, a correlative approach that enables subcellular antibiotic visualisation in pathogen-infected tissue is lacking. Here, we developed correlative light, electron, and ion microscopy in tissue (CLEIMiT) and used it to identify the cell type–specific accumulation of an antibiotic in lung lesions of mice infected with Mycobacterium tuberculosis. Using CLEIMiT, we found that the anti-tuberculosis (TB) drug bedaquiline (BDQ) is localised not only in foamy macrophages in the lungs during infection but also accumulate in polymorphonuclear (PMN) cells. Public Library of Science 2020-12-31 /pmc/articles/PMC7810513/ /pubmed/33382684 http://dx.doi.org/10.1371/journal.pbio.3000879 Text en © 2020 Fearns et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Methods and Resources
Fearns, Antony
Greenwood, Daniel J.
Rodgers, Angela
Jiang, Haibo
Gutierrez, Maximiliano G.
Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs
title Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs
title_full Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs
title_fullStr Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs
title_full_unstemmed Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs
title_short Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis–infected lungs
title_sort correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in mycobacterium tuberculosis–infected lungs
topic Methods and Resources
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810513/
https://www.ncbi.nlm.nih.gov/pubmed/33382684
http://dx.doi.org/10.1371/journal.pbio.3000879
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