Figure 1

Identification of PKIS compounds inhibiting intracellular growth of MRSA. (A) GFP-positive MRSA-infected HeLa cells were gated to determine the percentage of infected cells. (B) The DMSO control and 201 PKIS compounds were screened to assess their effect on MRSA bacterial burden, expressed as average z-scores of GFP-positive cells (z-score_MRSA+). (C) The 17 hit compounds with z-score_MRSA+ < -2 are shown. The screen was performed with three replicates for the PKIS compounds. Error bars represent standard deviations. (D) Structural resemblance of 4-anilino-quinazoline hit compounds with lapatinib. (E, F) The capacity of both PKIS1 (E) and PKIS2 (F) hit compounds to inhibit the HER kinase family is shown. Kinase inhibition data of HER3 were only available for PKIS2 compounds. (G, H) A comparison is made between hit compounds and non-hit PKIS compounds in their capacity to inhibit the human epidermal growth factor receptor (HER) kinase family. Bars and error bars show the median ± interquartile range. Each datapoint represents a PKIS compound. Statistical significance of observed differences was tested using Mann-Whitney tests (*p < 0.05; **p < 0.01; ***p < 0.001).