Faculty Opinions recommendation of Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages.

Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, remains the world's deadliest infectious disease. Sterilising chemotherapy requires at least six months of multidrug therapy. Difficulty visualising the subcellular localisation of antibiotics in infected host cells means that it is unclear whether antibiotics penetrate into all mycobacteria-containing compartments in the cell. Here, we combine correlated light, electron and ion microscopy to image the distribution of Bedaquiline in infected human macrophages at sub-micrometre resolution. Bedaquiline accumulated primarily in host cell lipid droplets, but heterogeneously in mycobacteria within a variety of intracellular compartments. Furthermore, lipid droplets did not sequester antibiotic but constituted a transferable reservoir that enhanced antibacterial efficacy. Thus, strong lipid binding facilitated drug trafficking by host organelles to an intracellular target during antimicrobial treatment.