Figure 4
From: Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria
Validation of PKIS hit compounds in cell lines and primary human macrophages. (a, b) The efficacy of the hit compounds was validated in CFU assays using lysates from Stm-infected HeLa cells (a) and Mtb-infected MelJuSo cells (b). The bacterial burden is expressed as a percentage of CFUs compared to the DMSO control. (c, d) Compound safety was assessed using an LDH-release assay with supernatant from Stm-infected HeLa cells (c) and Mtb-infected MelJuSo cells (d), with cell viability expressed as a percentage of the DMSO control and with 1% Triton X-100-treated cells corresponding to 0%. (e, f) To assess whether hit compounds act as antibiotics or host-directed therapeutics, direct antimicrobial effects were evaluated in cell-free cultures of Stm (e) and Mtb (f). The turbidity of the bacterial suspensions, as measured by absorbance at OD600, is given as a percentage of the DMSO control. (g) The efficacy of the hit compounds was validated in CFU assays using lysates from Stm-infected M1 (black circles, grey bars) and M2 (white circles, open bars) primary human macrophages. (h) An LDH-release assay was performed using supernatant from Stm-infected macrophages. (i) The efficacy of the hit compounds was validated in CFU assays using lysates from Mtb-infected M1 (black circles) and M2 (white circles) primary human macrophages. (j) An LDH-release assay was performed using supernatant from Mtb-infected macrophages.
