neutrophilic
METPO:1003001 · CLASS · REVIEWED
A pH growth preference characterized by optimal growth at near-neutral pH values, typically between pH 6.5 and 7.5.
Neutrophilic near-neutral pH homeostasis mechanism
Edge evidence
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near-neutral external pH
confers
neutrophilic
METPO:2007700Neutrophiles grow optimally when external pH is near neutrality.
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DOI:10.1038/nrmicro2549external pH values outside the cytoplasmic pH
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cytoplasmic pH homeostasis
confers
neutrophilic
METPO:2007700Growth near neutral pH still requires active maintenance of internal pH.
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DOI:10.1038/nrmicro2549bacterial pH homeostasis is a cell-wide physiological process
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proton motive force
interacts with
cytoplasmic pH homeostasis
biolink:interacts_withpH regulation is linked to proton motive force and bioenergetics.
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DOI:10.1016/j.tim.2007.02.005intrinsically linked to cellular bioenergetics
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cation/proton antiporter
contributes to
cytoplasmic pH homeostasis
RO:0002326Cation/proton antiporters help regulate ion and pH balance.
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DOI:10.3390/ijms21124566maintaining ion and pH homeostasis
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external acidic pH
increases
cytoplasmic proton influx
RO:0002213Low external pH increases H+ entry into the cytoplasm, challenging neutral pH homeostasis.
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DOI:10.1128/msystems.01037-23
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cytoplasmic buffering capacity
contributes to
intracellular pH
RO:0002326Proton sequestration by cytoplasmic buffers stabilizes intracellular pH and protects enzyme function.
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DOI:10.1128/msystems.01037-23
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amino-acid decarboxylation
contributes to
cytoplasmic pH homeostasis
RO:0002326Decarboxylation directly removes H+ from the cytoplasm, raising internal pH.
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DOI:10.3390/antibiotics12091474
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amino-acid decarboxylation
contributes to
proton motive force
RO:0002326Charge-differential substrate/product antiport plus proton consumption couples pH homeostasis to PMF generation.
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DOI:10.1093/femsre/fuad033
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F1F0-ATPase proton pump
contributes to
cytoplasmic pH homeostasis
RO:0002326ATP-dependent proton transport helps restore cytoplasmic pH under acid challenge.
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DOI:10.3390/antibiotics12091474
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Provenance
- Source
- METPO (2025-11-25)
- Author
- Anthea Guo
- Definition source
- DOI:10.1038/nrmicro2549
Parent traits (1)
Synonyms (3)
- neutralophile
- neutralophilic
- neutrophile
kg-microbe context
Matched 1 kg-microbe node via direct_metpo.
METPO:1003001[-2.302, -2.147, -2.266, -0.758, …]
Nearest neighbors in embedding space
- environment acidotolerant 0.980
- environment acidophilic 0.980
- environment obligately acidophilic 0.979
- environment alkaphilic 0.979
- environment obligately alkaphilic 0.979
- environment facultatively alkaphilic 0.979
- environment alkalotolerant 0.978
- environment facultatively acidophilic 0.975
Deep research
# Curation report: microbial **neutrophilic** trait ## 1. Scope and recommended interpretation **Target:** `METPO:1003001` **Label:** neutrophilic **Category:** ENVIRONMENT; **kind:** CLASS; **mapping:** REVIEWED **Operational definition supplied:** optimal growth near neutral pH, typically pH 6.5–7.5. The trait should represent a **growth-optimum phenotype**, not merely survival at neutral pH and not every mechanism activated during acid or alkaline shock. A foundational review uses *neutralophile* more broadly for bacteria capable of growth over approximately external pH 5.5–9.0 while generally maintaining cytoplasmic pH around 7.5–7.7. That broader growth range is compatible with, but should not replace, the supplied narrower optimum of pH 6.5–7.5. (krulwich2011molecularaspectsof pages 1-3) The central mechanistic interpretation is therefore: > near-neutral extracellular pH → modest transmembrane ΔpH and compatible proton-motive force → cytoplasmic pH maintained in the range required by enzymes and macromolecular processes → maximal or near-maximal population growth. This interpretation is supported by the observation that proteins have restricted functional pH ranges and that proton concentration is integral to cellular bioenergetics. In neutralophiles, cytoplasmic pH homeostasis and proton-motive-force management are thus proximal physiological requirements for growth. (krulwich2011molecularaspectsof pages 1-3) ### Boundary cases 1. **Acid tolerance is not neutrophily.** Enteric bacteria can survive gastric acidity without growing there; recovery after return to permissive pH measures survival, not an acidic growth optimum. Likewise, *S. aureus* growth at pH 4.5 is acid-stress adaptation, useful as mechanistic boundary evidence but not evidence that the organism’s defining optimum is acidic or neutral. (krulwich2011molecularaspectsof pages 1-3, beetham2024histidinetransportis pages 7-8) 2. **Alkali tolerance is not alkaliphily.** A 2024 Bacillus study classifies alkali-tolerant organisms as having optimal growth around pH 7–9 and failing above approximately 9.5, whereas alkaliphiles grow optimally around pH 10–12. Facultative alkaliphiles can grow near neutrality but retain an alkaline optimum. (maksimova2024metabolicandmorphological pages 1-2) 3. **Broad pH range does not establish the optimum.** Growth rates or yields must be measured across buffered pH values. Endpoint viability, metabolic dye reduction, ATP, or membrane integrity alone establish tolerance or physiological activity, not neutrophilic preference. 4. **“Neutrophile” is lexically hazardous.** In biomedical text it commonly denotes the leukocyte. For microbial curation, use **neutralophile**, **neutralophilic microorganism**, or the exact trait label **neutrophilic**, while excluding immune-cell records. 5. **pH is conditional.** Temperature, medium composition, aeration, salt, weak acids/bases, growth phase, and buffer chemistry can shift the measured optimum. The 2024 Bacillus work, for example, jointly varied pH and NaCl and found broader resistance in an alkaliphile, illustrating confounding by mineralization. (maksimova2024metabolicandmorphological pages 1-2, maksimova2024metabolicandmorphological pages 5-6) ## 2. Current mechanistic model and expert assessment Krulwich, Sachs, and Padan’s authoritative synthesis frames pH homeostasis as a coordinated system involving proton-motive force (PMF), primary proton pumps, ATPases, cation/proton antiporters, metabolic proton consumption or production, and envelope permeability. PMF comprises ΔpH and electrical potential Δψ; under standard conditions the review gives the approximation **PMF (mV) = Δψ − 59ΔpH**. Neutralophilic *E. coli* growing around pH 7 has only a small alkaline-inside ΔpH but a substantial negative-inside Δψ. (krulwich2011molecularaspectsof pages 1-3) This is not a single conserved “neutrophily pathway.” It is a **systems phenotype** emerging from ordinary cellular machinery tuned to keep cytoplasmic physicochemistry compatible with growth. The strongest universal graph core is consequently small: extracellular pH, cytoplasmic pH, ΔpH/Δψ, PMF, macromolecular function, and growth. Specific pumps, antiporters, decarboxylases, and envelope factors should be attached as taxon- and condition-specific branches rather than universal prerequisites. The source’s mechanistic figure independently depicts acid-challenged *E. coli* and *Streptococcus mutans*, and alkali-challenged *E. coli* and *Enterococcus hirae*. It confirms that the direction and identity of ATPase and ion-transport responses vary by organism and metabolic mode. (krulwich2011molecularaspectsof media 27b96047) ## 3. Candidate nodes grouped by type ### Trait and environmental nodes - **neutrophilic** — `METPO:1003001` - **parent trait** — `METPO:1003000` - near-neutral extracellular pH, pH 6.5–7.5 — label-only environmental/experimental condition - acidic challenge / low extracellular pH — label-only condition - alkaline challenge / high extracellular pH — label-only condition - sodium-poor condition — label-only experimental modifier - oxygen availability, medium buffer, temperature, NaCl concentration, weak organic acids — label-only covariates ### Cellular state, localization, and process nodes - cytoplasm — `GO:0005737` - plasma membrane — `GO:0005886` - cell wall — `GO:0005618` - cytoplasmic pH homeostasis — `GO:0030641` - proton transmembrane transport — `GO:1902600` - cellular response to pH — `GO:0071467` - growth / population growth — preferably use the project’s established microbial-growth term; otherwise label-only - proton-motive force, transmembrane ΔpH, membrane potential Δψ — label-only unless the project has an established electrochemical-gradient ontology - protein folding/function, enzyme activity, nutrient transport, ATP synthesis — GO grounding should be selected only at the granularity represented in the final graph ### Chemicals and metabolites - proton — `CHEBI:15378`
Curation history
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SEEDED_FROM_METPO · seed_from_metpo
imported from data/raw/metpo.owl (CLASS)
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CURATED_WITH_LITERATURE · codex
Reviewed neutrophilic trait and added DOI-backed evidence and causal graph for near-neutral pH homeostasis.
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GROUND_CAUSAL_PREDICATES · claude
Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002327×1, RO:0002326×1).
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GROUND_CAUSAL_PREDICATES · claude
Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:interacts_with×1).
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RENAME_PREDICATE_LABELS · claude
Renamed 1 causal-edge predicate label(s) to align with existing groundings: supports → enables ×1.
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GROUND_CAUSAL_PREDICATES · claude
Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002327×1).
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GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0030641×1).
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GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (METPO:1007500×1).
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GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A0H3JRG4×1).
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GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (PATO:0001432×1).
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RETYPE_CAUSAL_NODES · claude
Re-typed 1 causal-node node_type field(s) to align with CausalNodeTypeEnum semantics: proton motive force: BIOLOGICAL_PROCESS → STATE ×1.
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FIX_NODE_GROUNDING_CURIE · claude
Overwrote 1 causal-node grounding(s) (obsolete/wrong GO -> corrected, verified vs OAK).
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FIX_NODE_GROUNDING_CURIE · claude
Overwrote 1 pH causal-node grounding(s) to corrected PATO CURIEs (phase-2; verified vs OAK).
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ENRICH_CAUSAL_GRAPH · claude
Added 5 evidence-backed generic edges (6 new nodes) from the deep-research report.
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GROUND_CAUSAL_PREDICATES · claude
Grounded 5 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002326×4, RO:0002213×1).
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MIGRATE_ENABLES_TRAIT_EDGES · claude
Migrated 2 causal edge(s) off enables/RO:0002327 with a TRAIT object (2 to confers), issue 302. RO:0002327 has range 'biological process or activity', which a trait (a disposition) cannot satisfy, so the previous form entailed trait is-a BiologicalProcessOrActivity. The replacements are proposed in proposals/metpo_traitmech_v8 and are placeholder ids until METPO mints them.
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NORMALISE_NODE_TYPE · claude
Under the PATHWAY-vs-BIOLOGICAL_PROCESS rule, one node_id means one thing corpus-wide (issue 356): amino_acid_decarboxylation is typed BIOLOGICAL_PROCESS. PATHWAY is a named, conventionally enumerable multi-step route; BIOLOGICAL_PROCESS is everything else. A REACTION CLASS, not a route. The corpus describes it that way in neutrophilic.yaml -- 'Enzyme-catalyzed decarboxylation reaction that consumes cytoplasmic protons' -- and the wording varies by record, so read that as the family's sense rather than as this record's own text. Named systems that implement it (Gad) would be pathways; the reaction class is not. Was 4 BIOLOGICAL_PROCESS to 2 before this tranche.