Copper tolerance in bacteria requires the activation of multiple accessory pathways

Mol Microbiol. 2020 Sep;114(3):377-390. doi: 10.1111/mmi.14522. Epub 2020 May 19.


Copper is a required micronutrient for bacteria and an essential cofactor for redox-active cuproenzymes. Yet, excess copper is extremely toxic, and is exploited as a bacteriocide in medical and biotechnological applications and also by the mammalian immune system. To evade copper toxicity, bacteria not only control intracellular copper homeostasis, but they must also repair the damage caused by excess copper. In this review, we summarize the bacterial cell-wide response to copper toxicity in Enterobacteria. Tapping into the abundant research data on two key organisms, Escherichia coli and Salmonella enterica, we show that copper resistance requires both the direct copper homeostatic response and also the indirect accessory pathways that deal with copper-induced damage. Since patterns of copper response are conserved through the Proteobacteria, we propose a cell-wide view of copper detoxification and copper tolerance that can be used to identify novel targets for copper-based antibacterial therapeutics.

Keywords: copper; enterobacteria; escherichia; gram negative bacteria; homeostasis; salmonella.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / metabolism
  • Copper / metabolism*
  • Copper / toxicity*
  • Escherichia coli / physiology*
  • Homeostasis
  • Lipoproteins / metabolism
  • Membrane Transport Proteins / metabolism
  • Salmonella enterica / physiology*
  • Stress, Physiological


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carrier Proteins
  • Lipoproteins
  • Membrane Transport Proteins
  • copper-binding protein
  • Copper