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

PLoS Biol. 2020 Dec 31;18(12):e3000879. doi: 10.1371/journal.pbio.3000879. eCollection 2020 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents
  • Diarylquinolines / metabolism
  • Diarylquinolines / pharmacology
  • Female
  • Lung / cytology
  • Lung / diagnostic imaging*
  • Lung / microbiology
  • Male
  • Mice
  • Mice, Inbred C3H
  • Microbial Sensitivity Tests
  • Microscopy / methods*
  • Microscopy, Electron / methods
  • Mycobacterium tuberculosis / pathogenicity
  • Tuberculosis / diagnostic imaging*

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • bedaquiline