Copper Disposition in Bacteria

In the last two decades, there has been great advance in the understanding of bacterial copper homeostasis and toxicity mechanisms. A minimum of three proteins form the core of copper homeostasis in all bacteria: A copper-exporting ATPase that pumps copper across the cytoplasmic membrane, a copper chaperone, which sequesters and routes cytoplasmic copper, and a copper-responsive regulator that regulates the expression of these proteins. Gram-negative organisms possess additional components, such as copper export systems to traverse the outer membrane, periplasmic multicopper oxidases, and periplasmic copper chaperones. Recent work has also changed the understanding of copper toxicity. Rather than oxidative damage, copper's main toxic effect appears to lie in its ability to displace iron from iron–sulfur cluster proteins, thereby inactivating key enzymes. However, how cuproenzymes are metallated and how copper enters the bacterial cytoplasm is still poorly understood.