identifier: METPO:1003001
label: neutrophilic
definition: A pH growth preference characterized by optimal growth at near-neutral
  pH values, typically between pH 6.5 and 7.5.
definition_source: DOI:10.1038/nrmicro2549
trait_category: ENVIRONMENT
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1003000
synonyms:
- synonym_text: neutralophile
  synonym_type: EXACT_SYNONYM
  source: metpo.owl
- synonym_text: neutralophilic
  synonym_type: EXACT_SYNONYM
  source: metpo.owl
- synonym_text: neutrophile
  synonym_type: EXACT_SYNONYM
  source: metpo.owl
created_by: Anthea Guo
evidence:
- reference: DOI:10.1038/nrmicro2549
  snippet: cytoplasmic pH ... must maintain for growth
  notes: Supports pH growth preference as tied to cytoplasmic pH requirements.
canonical_examples:
- taxon_id: NCBITaxon:562
  taxon_label: Escherichia coli
  note: "grows optimally near pH 7"
  reference: DOI:10.1111/1574-6976.12076
- taxon_id: NCBITaxon:1423
  taxon_label: Bacillus subtilis
  note: "neutralophile"
  reference: PMID:24898062
causal_graphs:
- graph_id: neutrophilic_neutral_ph_homeostasis
  title: Neutrophilic near-neutral pH homeostasis mechanism
  description: Evidence-backed causal sketch linking neutrophilic growth to near-neutral
    external pH and ordinary cytoplasmic pH homeostasis.
  nodes:
  - node_id: neutrophilic_trait
    label: neutrophilic
    node_type: TRAIT
    grounding: METPO:1003001
    description: Optimal growth occurs at near-neutral pH.
  - node_id: near_neutral_external_ph
    label: near-neutral external pH
    node_type: ENVIRONMENTAL_FACTOR
    description: External pH around neutrality.
    grounding: PATO:0001428
  - node_id: cytoplasmic_ph_homeostasis
    label: cytoplasmic pH homeostasis
    node_type: BIOLOGICAL_PROCESS
    description: Maintenance of intracellular pH compatible with growth.
    grounding: GO:0051453
  - node_id: proton_motive_force
    label: proton motive force
    node_type: STATE
    description: Electrochemical proton gradient coupled to energy metabolism.
    grounding: METPO:1007500
  - node_id: cation_proton_antiporter
    label: cation/proton antiporter
    node_type: GENE_OR_PROTEIN
    description: Transporters contributing to ion and pH homeostasis.
    grounding: UniProtKB:A0A0H3JRG4
  - node_id: external_acidic_ph
    label: external acidic pH
    node_type: ENVIRONMENTAL_FACTOR
    description: Low external pH that challenges cytoplasmic pH homeostasis.
  - node_id: cytoplasmic_proton_influx
    label: cytoplasmic proton influx
    node_type: BIOLOGICAL_PROCESS
    description: Entry of protons into the cytoplasm across or through the membrane.
  - node_id: cytoplasmic_buffering_capacity
    label: cytoplasmic buffering capacity
    node_type: CAPACITY
    description: Proton sequestration by cytoplasmic buffers that dampens pH fluctuations.
  - node_id: intracellular_ph
    label: intracellular pH
    node_type: STATE
    description: The pH of the cytoplasm.
  - node_id: amino_acid_decarboxylation
    label: amino-acid decarboxylation
    node_type: BIOLOGICAL_PROCESS
    description: Enzyme-catalyzed decarboxylation reaction that consumes cytoplasmic
      protons.
  - node_id: f1f0_atpase_proton_pump
    label: F1F0-ATPase proton pump
    node_type: GENE_OR_PROTEIN
    description: ATP-dependent proton transporter contributing to pH restoration.
  edges:
  - subject: near_neutral_external_ph
    predicate: enables
    object: neutrophilic_trait
    description: Neutrophiles grow optimally when external pH is near neutrality.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      snippet: external pH values outside the cytoplasmic pH
      notes: Review supports growth constraints around cytoplasmic pH compatibility.
    predicate_id: RO:0002327
  - subject: cytoplasmic_ph_homeostasis
    predicate: enables
    object: neutrophilic_trait
    description: Growth near neutral pH still requires active maintenance of internal
      pH.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      snippet: bacterial pH homeostasis is a cell-wide physiological process
      notes: Supports pH homeostasis as central to bacterial growth.
    predicate_id: RO:0002327
  - subject: proton_motive_force
    predicate: interacts with
    object: cytoplasmic_ph_homeostasis
    description: pH regulation is linked to proton motive force and bioenergetics.
    evidence:
    - reference: DOI:10.1016/j.tim.2007.02.005
      snippet: intrinsically linked to cellular bioenergetics
      notes: Supports coupling of pH gradients and bioenergetics.
    predicate_id: biolink:interacts_with
  - subject: cation_proton_antiporter
    predicate: contributes to
    object: cytoplasmic_ph_homeostasis
    description: Cation/proton antiporters help regulate ion and pH balance.
    evidence:
    - reference: DOI:10.3390/ijms21124566
      snippet: maintaining ion and pH homeostasis
      notes: Supports cation/proton antiport as a general pH-homeostasis mechanism.
    predicate_id: RO:0002326
  - subject: external_acidic_ph
    predicate: increases
    object: cytoplasmic_proton_influx
    description: Low external pH increases H+ entry into the cytoplasm, challenging
      neutral pH homeostasis.
    evidence:
    - reference: DOI:10.1128/msystems.01037-23
      notes: At low pH, H+ can permeate into the cytoplasm via protonated water chains,
        ion channels, or damaged membranes (general for neutralophilic bacteria).
    predicate_id: RO:0002213
  - subject: cytoplasmic_buffering_capacity
    predicate: contributes to
    object: intracellular_ph
    description: Proton sequestration by cytoplasmic buffers stabilizes intracellular
      pH and protects enzyme function.
    evidence:
    - reference: DOI:10.1128/msystems.01037-23
      notes: Protons can be sequestered by side-chains of proteins, inorganic phosphates,
        polyphosphates, or polyamines (general for neutralophiles).
    predicate_id: RO:0002326
  - subject: amino_acid_decarboxylation
    predicate: contributes to
    object: cytoplasmic_ph_homeostasis
    description: Decarboxylation directly removes H+ from the cytoplasm, raising internal
      pH.
    evidence:
    - reference: DOI:10.3390/antibiotics12091474
      notes: The decarboxylation of amino acids is an enzyme-catalyzed reaction that
        consumes protons (general acid-tolerance mechanism in neutralophiles).
    predicate_id: RO:0002326
  - subject: amino_acid_decarboxylation
    predicate: contributes to
    object: proton_motive_force
    description: Charge-differential substrate/product antiport plus proton consumption
      couples pH homeostasis to PMF generation.
    evidence:
    - reference: DOI:10.1093/femsre/fuad033
      notes: The chemistry of the decarboxylation reaction requires a proton, and
        the equivalent of 1 proton is pumped per molecule decarboxylated (general
        mechanism).
    predicate_id: RO:0002326
  - subject: f1f0_atpase_proton_pump
    predicate: contributes to
    object: cytoplasmic_ph_homeostasis
    description: ATP-dependent proton transport helps restore cytoplasmic pH under
      acid challenge.
    evidence:
    - reference: DOI:10.3390/antibiotics12091474
      notes: Common mechanisms involved in bacterial acid tolerance include the F1-F0-ATPase
        proton pump (general).
    predicate_id: RO:0002326
curation_history:
- timestamp: '2026-05-05T01:35:46.937067+00:00'
  curator: seed_from_metpo
  action: SEEDED_FROM_METPO
  changes: imported from data/raw/metpo.owl (CLASS)
  llm_assisted: false
- timestamp: '2026-05-11T00:00:00-07:00'
  curator: codex
  action: CURATED_WITH_LITERATURE
  changes: Reviewed neutrophilic trait and added DOI-backed evidence and causal graph
    for near-neutral pH homeostasis.
  llm_assisted: true
- timestamp: '2026-05-20T03:35:30Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002327×1, RO:0002326×1).
  llm_assisted: true
- timestamp: '2026-05-20T05:49:24Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (biolink:interacts_with×1).
  llm_assisted: true
- timestamp: '2026-05-24T04:13:18Z'
  curator: claude
  action: RENAME_PREDICATE_LABELS
  changes: 'Renamed 1 causal-edge predicate label(s) to align with existing groundings:
    supports → enables ×1.'
  llm_assisted: true
- timestamp: '2026-05-24T04:13:21Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002327×1).
  llm_assisted: true
- timestamp: '2026-05-24T04:38:00Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (GO:0030641×1).
  llm_assisted: true
- timestamp: '2026-05-24T04:41:03Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (METPO:1007500×1).
  llm_assisted: true
- timestamp: '2026-05-24T05:05:14Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A0H3JRG4×1).
  llm_assisted: true
- timestamp: '2026-05-24T08:14:32Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (PATO:0001432×1).
  llm_assisted: true
- timestamp: '2026-05-26T02:30:12Z'
  curator: claude
  action: RETYPE_CAUSAL_NODES
  changes: 'Re-typed 1 causal-node node_type field(s) to align with CausalNodeTypeEnum
    semantics: proton motive force: BIOLOGICAL_PROCESS → STATE ×1.'
  llm_assisted: true
- timestamp: '2026-06-15T07:20:36Z'
  curator: claude
  action: FIX_NODE_GROUNDING_CURIE
  changes: Overwrote 1 causal-node grounding(s) (obsolete/wrong GO -> corrected, verified
    vs OAK).
  llm_assisted: true
- timestamp: '2026-06-15T07:21:43Z'
  curator: claude
  action: FIX_NODE_GROUNDING_CURIE
  changes: Overwrote 1 pH causal-node grounding(s) to corrected PATO CURIEs (phase-2;
    verified vs OAK).
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 5 evidence-backed generic edges (6 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:10Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 5 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002326×4, RO:0002213×1).
  llm_assisted: true