Extended Data Fig. 8: Treating E. coli with an IspH inhibitor prodrug disrupts the levels of IspH and several proteins in essential bacterial metabolic and synthesis pathways.
From: RETRACTED ARTICLE: IspH inhibitors kill Gram-negative bacteria and mobilize immune clearance
a, Immunoblots measure relative levels of E. coli IspH at 8 and 24 h after C23.28–TPP treatment or after conditional knockdown in CGSC 8074 (ΔispH) grown on 1% glucose. b, Immunoblots measure relative levels of IspH in clinical isolates of several pathogenic bacteria at 8 and 24 h after C23.28–TPP treatment. For a, b, RpoD immunoblot serves as loading control and the blots are representative of 3 technical replicates. c, Unsupervised hierarchical clustering of 2,346 proteins resolved indicates that the 3 biological replicates for each condition clustered together. A total of 525 proteins were either up- or downregulated both after C23.28–TPP treatment or after conditional knockdown in CGSC 8074 (ΔispH). d, Functions or pathways that are significantly enriched 8 and 24 h after C23.28–TPP treatment. Bars indicate the −log10(P value) with the number of proteins identified in each category next to the respective bar. The bars are colour-coded for the percentage of proteins in the pathway that are up- or downregulated. e, Venn diagram comparing the overlap in downregulated (>2-fold) proteins at 8 or 24 h after C23.28–TPP treatment or after conditional knockdown in CGSC 8074 (ΔispH). f, Proteins important for lipid synthesis, ribosome modification, respiration, cell division, tRNA aminoacylation, DNA/RNA synthesis, DNA repair, amino acid (AA) synthesis and lipopolysaccharide (LPS) cell-wall synthesis pathways are among those significantly downregulated. Associated with Extended Data Fig. 9a. P < 0.05 and FDR < 5%. g, Venn diagram comparing the overlap in upregulated (>2-fold) proteins at 8 or 24 h after C23.28–TPP treatment or after conditional knockdown in CGSC 8074 (ΔispH). h, Ribosome component proteins or proteins important for multidrug efflux and oxidative defence pathways are among those significantly upregulated. Associated with Extended Data Fig. 9b. P < 0.05 and FDR <5%.
