Advances in understanding of the copper homeostasis in Pseudomonas aeruginosa

Lukas Hofmann, Melanie Hirsch, Sharon Ruthstein

Research output: Contribution to journalReview articlepeer-review


Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the U.S. Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens.

Original languageEnglish
Article number2050
Pages (from-to)1-23
Number of pages23
Issue number4
StatePublished - 19 Feb 2021


  • Antibiotic resistance
  • CopRS
  • Copper homeostasis
  • CueR
  • CusCBA
  • Multidrug resistance
  • Pathogen
  • Pseudomonas aeruginosa
  • Transcription factors
  • Transcription regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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