Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in Mycobacterium tuberculosis-infected lungs.
Antony FearnsDaniel J GreenwoodAngela RodgersHaibo JiangMaximiliano G GutierrezPublished in: PLoS biology (2020)
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.
Keyphrases
- mycobacterium tuberculosis
- electron microscopy
- single molecule
- high resolution
- drug resistant
- high speed
- pulmonary tuberculosis
- multidrug resistant
- optical coherence tomography
- high throughput
- induced apoptosis
- label free
- cell cycle arrest
- solar cells
- endoplasmic reticulum stress
- emergency department
- high fat diet induced
- cell proliferation
- oxidative stress
- human immunodeficiency virus
- hiv infected
- reactive oxygen species
- cell death
- skeletal muscle
- hepatitis c virus