Fig. 7. Fumarate regulates EHEC virulence through the Cra transcription factor.

a The survival of N2 worms fed with the wild-type strain (EDL933) and the isogenic deletion strains of sdhA (EDL933:ΔsdhA), the sdhA and cra double mutant (EDL933:ΔsdhAΔcra) and mutants treated with 2.5 mM fumarate, respectively (EDL933:ΔsdhA + Fumarate and ΔsdhAΔcra + Fumarate) were examined. The virulence of sdhA and cra double mutant treat with 2.5 mM fumarate (EDL933:ΔsdhAΔcra + Fumarate, median N2 lifespan = 10.3 ± 0.9 days) was similar to sdhA mutant treated with 2.5 mM fumarate (EDL933:Δ sdhA + Fumarate, median N2 lifespan = 6.3 ± 0.3 days, P < 0.0001). The asterisk denotes statistically significant (P < 0.0001) examined by the log-rank test and “ns” represents no significant difference statistically. b A schematic model illustrating the roles of aerobic metabolism (aerobic respiration and TCA cycle), succinate dehydrogenaae (SdhA), and especially the metabolite, fumarate, in controlling the virulence of EHEC through a TnaA- and Cra-dependent manner