Fig 1

Fig 1

Identification of amiodarone as host-directed therapeutic for mycobacterial infections in primary human macrophages. (A) Chemical structure of amiodarone HCl (AMD). (B) Mtb H37Rv-infected M1 and M2 macrophages were treated for 24 hours with 10 µM amiodarone or an equal volume of vehicle control dimethyl sulfoxide (DMSO). Cells were subsequently lysed and bacterial survival was determined by CFU assay. Bacterial survival data represent the mean ± standard deviation (SD) from different donors (n = 9 or 10). Dots represent the mean from triplicate wells of a single donor. Bacterial survival is expressed as the percentage of vehicle control DMSO (=100%, indicated with the dotted line) per donor. Statistical significance was tested using a paired t-test. (C) Growth of Mtb H37Rv in liquid broth was monitored for 10 days after exposure to positive control 20 µg/mL rifampicin (RIF), 10 µM amiodarone, or vehicle control DMSO. Data represent the mean ± SD of triplicate wells from three independent experiments. (D) Bacterial survival of Mav within M1 and M2 macrophages after treatment for 24 hours with 10 µM amiodarone or an equal volume of vehicle control DMSO. Cells were subsequently lysed and bacterial survival was determined by mycobacteria growth indicator tube (MGIT) assay. Data represent the mean ± SD from different donors (n = 11 or 12). Dots represent the mean from triplicate wells of a single donor. Bacterial survival is expressed as the percentage of vehicle control DMSO (=100%, indicated with the dotted line) per donor. Statistical significance was tested using a paired t-test. (E) Growth of Mav in liquid broth was monitored for 10 days after exposure to positive control 100 µg/mL kanamycin (KANA), 10 µM amiodarone, or vehicle control DMSO. Data represent the mean ± SD of triplicate wells from three independent experiments. (F) Percentage of viable M1 and M2 macrophages [based on lactate dehydrogenase (LDH) release] after 24 hours of treatment with 10 µM amiodarone or an equal volume of vehicle control DMSO (0.1%, vol/vol). Data represent the mean ± SD from different donors (n = 2). *P < 0.05, **P < 0.01, and ****P < 0.0001.