FIG 6.

Proposed model for regulation and contribution of PmtA to GAS pathogenesis. In wild-type GAS (left), iron released from Fe-S cluster-containing proteins by ROS stress causes an increase in the GAS intracellular iron concentration. As a result, the iron-metallated form of PerR senses ROS, and oxidized PerR (Oxi-PerR) causes the derepression of pmtA by its dissociation from the pmtA promoter. PmtA aids GAS antioxidant defense by exporting iron out of the cytosol using the energy derived from ATP hydrolysis. In the ΔpmtA mutant, a failure to prevent the cytosolic accumulation of iron results in increased sensitivity to oxidative stress, increased oxidative damage, reduced bacterial survival, and attenuated GAS virulence.