Fig. 6: The HitRS activator ‘205 diverts cellular metabolism from aerobic respiration to fermentation.

A Volcano plot showing transcriptomic comparison between ‘205 (50 µM) and vehicle treatments of B. anthracis WT. Genes significantly upregulated or downregulated following ‘205 treatment are highlighted in orange or blue, respectively. The fold change cutoff is ≥3 and the P value cutoff is <0.05, both of which are indicated by gray lines. B Genes identified in the RNA-seq analysis with significantly differential expression grouped into predicted functional categories. C A subset of notable metabolic pathways that showed significantly different expression following ‘205 treatment: glycolysis, gluconeogenesis, and TCA cycle. Products of genes with increased expression are labeled in orange while the ones with decreased expression are labeled in blue. The fold change of each specific gene is indicted: +, upregulation; −, downregulation. D Ethanol concentration was quantified in the spent media of WT cell cultures in the absence or presence of 50 µM ‘205. ‘205 drives glucose metabolism towards pyruvate fermentation, resulting in higher level of ethanol compared to vehicle control. Data shown are three independent experiments with three replicates each time (mean ± SEM; n = 9). Significant differences are determined by two-tailed t tests.