identifier: traitmech:000018
label: copper tolerant
definition: A metal tolerance in which an organism grows in the presence of elevated
  copper (Cu2+/Cu+) concentrations, typically via the cue, cus, pco, and cop systems
  and ATPase-driven cytoplasmic copper efflux.
definition_source: DOI:10.1007/s10565-013-9262-1
trait_category: ENVIRONMENT
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- traitmech:000012
synonyms:
- synonym_text: copper resistant
  synonym_type: RELATED_SYNONYM
  source: DOI:10.1007/s10565-013-9262-1
evidence:
- reference: DOI:10.1007/s10565-013-9262-1
  snippet: ATPase-driven copper efflux seems to be the main mechanism responsible
    for cytoplasmic copper detoxification in until now studied bacteria
  notes: Review supports active efflux via the cue, cus, pco, and cop systems as the
    basis of bacterial copper tolerance.
- reference: DOI:10.3389/fmicb.2020.00047
  snippet: C. metallidurans BS1 conferred resistance to Zn2+ displaying a MIC of 20
    mM, Cd2+ (2.5 mM), Co2+ (20mM), Ni2+ (8 mM), As3+ (3.5 mM), Cu2+ (5 mM), Au3+
    (1 uM) and Pb2+ (1.7 mM)
  notes: 'Organism example: Cupriavidus metallidurans BS1 tolerates copper (Cu2+)
    to a MIC of 5 mM.'
canonical_examples:
- taxon_id: NCBITaxon:119219
  taxon_label: Cupriavidus metallidurans
  note: "copper-resistance determinants"
  reference: PMID:37191542
causal_graphs:
- graph_id: copper_tolerance_cop_efflux
  title: Copper tolerance via cop/cue/cus/pco efflux systems
  description: Evidence-backed causal sketch linking dedicated copper-efflux machinery
    to cytoplasmic copper detoxification.
  nodes:
  - node_id: copper_tolerant_trait
    label: copper tolerant
    node_type: TRAIT
    grounding: traitmech:000018
    description: Capacity to grow at elevated Cu(I)/Cu(II) concentrations.
  - node_id: copper_ion
    label: copper(2+) ion
    node_type: CHEMICAL
    grounding: CHEBI:29036
    description: Cytoplasmic Cu(II) excess threatening Fenton-like damage.
  - node_id: copper_efflux_system
    label: copper efflux systems (cue/cus/pco/cop)
    node_type: GENE_OR_PROTEIN
    description: ATPase- and RND-driven pumps removing copper from the cytoplasm or
      periplasm.
  - node_id: copper_transport
    label: copper ion transmembrane transport
    node_type: BIOLOGICAL_PROCESS
    grounding: GO:0035434
    description: Active export of copper ions across the cytoplasmic membrane.
  - node_id: ros_oxidative_damage
    label: ROS-mediated oxidative damage
    node_type: BIOLOGICAL_PROCESS
    description: Fenton-like Cu(I) chemistry generating ROS that damage lipids, proteins,
      DNA, and Fe-S clusters.
  - node_id: multicopper_oxidase
    label: periplasmic multicopper oxidase (CueO-type)
    node_type: GENE_OR_PROTEIN
    description: Oxygen-dependent multicopper oxidase that oxidizes toxic Cu(I) to
      less-toxic Cu(II) in the periplasm.
  - node_id: cu1_oxidation
    label: Cu(I) to Cu(II) oxidation
    node_type: MOLECULAR_FUNCTION
    description: Enzymatic oxidation of toxic cuprous Cu(I) to less-toxic cupric Cu(II)
      reducing ROS-mediated damage.
  edges:
  - subject: copper_ion
    predicate: challenges
    object: copper_tolerant_trait
    description: Elevated cytoplasmic copper is the toxic challenge the trait counters.
    evidence:
    - reference: DOI:10.3389/fmicb.2020.00047
      notes: Cupriavidus metallidurans BS1 tolerates Cu(2+) to a MIC of 5 mM.
    predicate_id: METPO:2007406
  - subject: copper_efflux_system
    predicate: enables
    object: copper_transport
    description: Cue/cus/pco/cop pumps drive ATPase-mediated copper export.
    evidence:
    - reference: DOI:10.1007/s10565-013-9262-1
      notes: Review supports ATPase-driven efflux via cue/cus/pco/cop systems as the
        main copper detoxification mechanism.
    predicate_id: RO:0002327
  - subject: copper_transport
    predicate: mitigates
    object: copper_ion
    description: Copper export depletes the cytoplasmic copper pool.
    evidence:
    - reference: DOI:10.1007/s10565-013-9262-1
      notes: Cytoplasmic copper detoxification is the basis of bacterial copper tolerance.
    predicate_id: METPO:2007407
  - subject: copper_ion
    predicate: causes
    object: ros_oxidative_damage
    description: Excess intracellular copper drives Fenton-like reactions producing
      ROS that damage cellular macromolecules.
    evidence:
    - reference: DOI:10.3390/antibiotics12091474
      notes: Cu(I) driving Fenton-like reactions causing damage to lipids, proteins
        and DNA and disrupting Fe-S clusters; defines why tolerance mechanisms matter.
    predicate_id: biolink:causes
  - subject: copper_transport
    predicate: mitigates
    object: ros_oxidative_damage
    description: P1B-type ATPase copper efflux lowers cytoplasmic copper, reducing
      copper-driven oxidative toxicity.
    evidence:
    - reference: DOI:10.3390/antibiotics12091474
      notes: Primary defense is active efflux via P1B-1 (P-type) ATPases; in Gram-negatives
        CopA pumps cytoplasmic Cu(I) to the periplasm, decreasing cytoplasmic copper
        toxicity.
    predicate_id: METPO:2007407
  - subject: multicopper_oxidase
    predicate: enables
    object: cu1_oxidation
    description: CueO-type periplasmic multicopper oxidase catalyzes oxidation of
      Cu(I) to Cu(II) in the presence of oxygen.
    evidence:
    - reference: DOI:10.3390/antibiotics12091474
      notes: CueO oxidizes Cu(I) to less-toxic Cu(II) in oxygen; generalized periplasmic
        detox mechanism (aerobic context).
    predicate_id: RO:0002327
  - subject: cu1_oxidation
    predicate: mitigates
    object: copper_ion
    description: Oxidation of Cu(I) to less-toxic Cu(II) lowers the reactive copper
      burden in the periplasm.
    evidence:
    - reference: DOI:10.3390/antibiotics12091474
      notes: Oxidation of Cu(I) to less-toxic Cu(II) reduces reactive-copper toxicity
        and ROS-mediated membrane damage.
    predicate_id: METPO:2007407
curation_history:
- timestamp: '2026-05-28T00:00:00Z'
  curator: claude
  action: PROPOSED_FROM_RESEARCH
  changes: Proposed candidate ENVIRONMENT trait (copper tolerance) from literature
    research; metal-specific sub-variant of metal tolerant.
  llm_assisted: true
- timestamp: '2026-06-09T14:00:00Z'
  curator: claude
  action: CURATED_CAUSAL_GRAPH
  changes: Added evidence-backed causal graph (cop/cue/cus/pco copper efflux) with
    CHEBI/GO node groundings and RO/METPO predicate groundings; promoted PROPOSED
    to REVIEWED.
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 4 evidence-backed generic edges (3 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:09Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 4 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2007407×2, biolink:causes×1, RO:0002327×1).
  llm_assisted: true