Human PXR activation in hMDMs leads to drug nonresponsiveness.
A, intracellular survival assay of M. tuberculosis H37Rv, exposed to an incremental concentration of rifampicin (0.025 to 1 μg/ml) in the presence and absence of ketoconazole in control and PXR overexpressing hMDMs. B, CYP3A4-XREM promoter reporter assay in COS1 cells overexpressing hPXR treated with different concentrations of rifampicin (0.025 to 1 μg/ml) in the presence or absence of ketoconazole. C and D, intracellular survival of rifampicin-sensitive (C) and rifampicin-resistant (D) M. tuberculosis as monitored by CFU assay in control, PXR knockdown, and PXR overexpressing hMDMs in the presence or absence of 0.25 μg/ml of rifampicin for 48 h. Data are mean ± S.D. from three independent experiments each performed in triplicate. *, p < 0.05 compared with control or as indicated.