HDAC inhibitors decrease Mtb survival in human macrophages in a host-directed manner. (A) Schematic outline of the experimental setup used in (B). (B) Mϕ1 and Mϕ2 macrophages derived from 11 different donors were infected with Mtb for 1 h at MOI 10 and treated with TMP195 (10 μM), TMP269 (10 μM), TSA (100 nM), or DMSO at equal v/v for 48 h post-infection. Dots represent the mean of 3 CFU assay replicates of a single donor expressed as a percentage of the DMSO control. Horizontal lines indicate median CFU values of all 11 donors and whiskers represent 95% confidence intervals. Statistically significant differences compared to DMSO were tested using a RM one-way ANOVA (**p < 0.01, ****p < 0.0001). (C) Thirteen days treatment of a Mtb broth culture in the presence of 10 μM TMP195, TMP269, or TSA. Rifampicin (20 μg/ml) was used as a positive control. Bars depict the mean bacterial density at 550 nm ± standard deviation of six replicates from a representative experiment out of two independent experiments. The bacterial load is expressed as a percentage of the DMSO control value. Statistically significant difference compared to DMSO was tested using a one-way ANOVA with Dunnett's multiple test correction (****p < 0.0001).
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