Fig. 5: Clinical isolates exhibit adaptive metabolic changes to itaconate.

a Non-synonymous mutations (NSMs) in the genomes of clinical isolates. REF represents a reference isolate from the same patient. b Expression of central carbohydrate metabolic genes and c stress response genes by the clinical isolates, with respect to LAC. d Utilization of carbon sources that feed glycolysis (blue), EPS synthesis (purple), fermentation (green), or the TCA cycle (orange) by the earliest (A 2001) and latest (T 2015) clinical isolates. e Growth of clinical isolates in LB. f Biofilm production (normalized for growth) of the clinical isolates in increasing itaconate (0 to 62 mM), with or without glucose (0.5%). Data shown as mean ± SEM from n = 3 biological replicates from 3 independent experiments (b, c, d, e, f). Significance determined by One-Way ANOVA with Tukey’s Multiple Comparisons (b, c); *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.