Fig. 2: sAEL057 treatment leads to dysregulation of genes involved in iron homeostasis and cholesterol metabolism in Mtb.
From: Iron limitation in M. tuberculosis has broad impact on central carbon metabolism
a PCA analysis of Mtb transcriptomes from infected HMDMs. b, c Heatmaps showing relative expression of genes in the KstR1 regulon. d, e Heatmaps showing relative expression of genes involved with iron homeostasis. a, b, d, f, h, j, l HMDMs were infected at MOI 2:1 for 2 days with mCherry-expressing Mtb prior to administration of sAEL057 at 10 µM. Infected macrophages were sorted for mCherry positivity 2 days after sAEL057 treatment was commenced, at 4 dpi. Samples were sorted into triazole prior to RNA extraction. c, d, g, i, k, m Mtb was pre-grown in cholesterol-supplemented media (7H9 + cholesterol) for 2 days prior to the addition of sAEL057 at 10x MIC (23 µM). Samples were collected at 4 h posttreatment for RNA extraction. Normalized counts were used for the generation of all heatmaps. f–m Violin plots showing expression (in log normalized counts) of genes encoding for HsaC, FadE29, BfrB, and MbtI in the two environmental conditions. Statistical significance values based on adjusted P values (padj) in Supplementary Data 1 for respective genes.
