FIG 7.

Threshold model for bacterial Cu homeostasis, tolerance, and stress. As Cu levels in the cytoplasm increase, this metal ion binds to the allosteric site of the Cu-sensing transcriptional regulator, which subsequently induces expression of the Cu efflux pump. Together, the Cu sensor and efflux pump impose a low limit of Cu availability and maintain Cu homeostasis. A further rise in cytoplasmic Cu levels saturates the Cu homeostasis system and begins to fill binding sites in GSH. Since there are no observable defects in bacterial metabolism or growth at this stage, GSH can be considered to confer Cu tolerance. GSH depletion or a further increase in cytoplasmic Cu levels saturates this tolerance capacity. Cu now binds to noncognate metal-binding sites, leading to inhibition of bacterial metabolism and growth. These conditions are considered as Cu stress.