FIGURE 7.

Proposed model for the P. aeruginosa heme cell surface signaling system. A, in the absence of heme HasR binds the HasI σ-factor inhibiting its activity. B, in the presence of heme HasA binds to HasR initiating TonB-dependent import of heme into the cell and signaling displacement of the anti-σ factor, freeing HasI for increased expression of the heme uptake systems. Positive regulation of HasS allows inactive HasS to accumulate so that as extracellular heme levels decrease, HasI can be inactivated to rapidly down-regulate the Phu and Has heme uptake systems.