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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Main Authors: Antony Fearns, Daniel J Greenwood, Angela Rodgers, Haibo Jiang, Maximiliano G Gutierrez
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-12-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3000879
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spelling doaj-d4d0c9db78524b23a0be687787c9ab2f2021-07-02T17:09:57ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852020-12-011812e300087910.1371/journal.pbio.3000879Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis-infected lungs.Antony FearnsDaniel J GreenwoodAngela RodgersHaibo JiangMaximiliano G GutierrezCorrelative 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.https://doi.org/10.1371/journal.pbio.3000879
collection DOAJ
language English
format Article
sources DOAJ
author Antony Fearns
Daniel J Greenwood
Angela Rodgers
Haibo Jiang
Maximiliano G Gutierrez
spellingShingle Antony Fearns
Daniel J Greenwood
Angela Rodgers
Haibo Jiang
Maximiliano G Gutierrez
Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis-infected lungs.
PLoS Biology
author_facet Antony Fearns
Daniel J Greenwood
Angela Rodgers
Haibo Jiang
Maximiliano G Gutierrez
author_sort Antony Fearns
title 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_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_sort correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in mycobacterium tuberculosis-infected lungs.
publisher Public Library of Science (PLoS)
series PLoS Biology
issn 1544-9173
1545-7885
publishDate 2020-12-01
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.
url https://doi.org/10.1371/journal.pbio.3000879
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