Bioorthogonal Correlative Light-Electron Microscopy of <i>Mycobacterium tuberculosis</i> in Macrophages Reveals the Effect of Antituberculosis Drugs on Subcellular Bacterial Distribution
Thomas Bakkum, Matthias T. Heemskerk, Erik Bos, Mirjam G. J. Groenewold, Nikolaos Oikonomeas‐Koppasis, Kimberley V. Walburg, Suzanne van Veen, Martijn J. C. van der Lienden, Tyrza van Leeuwen, Mariëlle C. Haks, Tom H. M. Ottenhoff, Abraham J. Koster, Sander I. van Kasteren
Abstract
). The RNA polymerase-targeting drug rifampicin displayed the most prominent effect on subcellular distribution, suggesting the most direct effect on pathogenicity and/or viability, while the cell wall synthesis-targeting drugs isoniazid and ethambutol effectively rescued bacterial division-induced loss of metabolic labels. The three drugs combined did not give a more pronounced effect but rather an intermediate response, whereas gentamicin displayed a surprisingly strong additive effect on subcellular distribution.