FIGURE 8.

Model summarizing effects of aconitase or superoxide dismutase deletion on STM physiology. Deletion of aconitases disrupts the TCA cycle, leading to citrate and, by an unknown mechanism, isocitrate accumulation. Citrate acts as chelator of iron, among other ions, which reacts in Fenton and Haber-Weiss reactions to HR. Increased ROS concentration induce stress regulons, minimizing effects of ROS damage. Deletion of cytosolic superoxide dismutases leads to ROS stress by accumulating SOA. SOA dismutate in part to HPO. Both kinds of ROS damage Fe–S clusters and form with liberated iron ions HR. Although stress response proteins are induced, continuous oxidative stress overwhelms the capacity of ROS-detoxifying enzymes. Beside reduced expression of acnA, ROS attack Fe–S clusters, including those of aconitases, mediating citrate accumulation and downstream effects similar to those observed in STM ΔacnAB. In STM ΔsodAB ROS from both sources damage macromolecules like DNA, which reduces bacterial viability.