Abstract
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.
Highlights
An effective chemotherapy against bacterial infections must include antibiotics with pharmacokinetic properties that together allow penetration into all infected microenvironments [1]
Lungs were removed and granulomatous lesions were visualised by micro-computed tomography
In agreement with previous studies, we found that granulomatous lesions were heavily enriched in lipid droplet (LD)-laden foamy macrophages (Fig 1B and 1C)
Summary
An effective chemotherapy against bacterial infections must include antibiotics with pharmacokinetic properties that together allow penetration into all infected microenvironments [1]. Antimicrobial penetration is especially important for the treatment of infections where antibiotics need to reach intracellular bacteria [2], including Mycobacterium tuberculosis. It is critical to define if antimicrobials are able to reach their intracellular targets, imaging of antibiotics (and drugs in general) at the subcellular level in infected tissues remains challenging. Recently have studies in vivo determined antibiotic distributions in granulomatous lesions by matrix-assisted laser desorption–ionisation mass spectrometric imaging (MALDI-MSI) [5]. This approach only allows analysis at the tissue level and does not reach subcellular or even cellular resolution [6].
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