pH range mid1

METPO:1000461 · CLASS · REVIEWED

A pH range phenotype in which the growth-supporting external pH range spans approximately 6–7, characteristic of neutrophilic physiology.

pH-range-mid1 neutrophile range

DOI-backed graph linking baseline pH-homeostasis at near-neutral external pH to a pH growth range of approximately 6–7.

pH-range-mid1 neutrophile range Interactive directed graph showing evidence-backed causal relationships for pH range mid1.

Edge evidence

  • baseline pH homeostasis confers pH range mid1 METPO:2007700

    Baseline pH-homeostasis enables growth across pH 6–7.

    • DOI:10.1038/nrmicro2549 pH homeostasis Supports baseline pH-homeostasis as the neutrophilic range mechanism.
  • pH range mid1 is a pH range rdfs:subClassOf

    pH range mid1 is a quantitative bin of the pH-range phenotype.

    • DOI:10.1038/nrmicro2549 external pH Supports the pH 6–7 range as a value within the pH-range distribution.
  • proton motive force enables cytoplasmic pH homeostasis RO:0002327

    PMF (membrane potential) is required to maintain cytoplasmic pH homeostasis.

    • DOI:10.1103/PRXLife.2.043015 Terradot et al. 2024: decreasing the PMF's strength impairs the cells' ability to maintain pH.
  • cytoplasmic pH homeostasis confers pH range mid1 METPO:2007700

    Maintaining near-neutral cytoplasmic pH supports the neutrophilic pH 6-7 growth range.

    • DOI:10.1103/PRXLife.2.043015 Cytoplasmic pH held near neutral underlies the neutralophile growth range.
  • cation/proton antiporters determines cytoplasmic pH homeostasis

    Transporter repertoire (ClcA/NhaB/NhaA-like antiporters) sets the external-pH boundaries over which cytoplasmic pH ~7 is maintained.

    • DOI:10.1103/PRXLife.2.043015 Terradot et al. 2024: ClcA-like ~pHe 2-5, NhaB-like ~5-9, NhaA-like ~9-12 maintain pHi ~7.
  • acid challenge positively regulates respiratory proton-pumping complexes RO:0002213

    Under acid challenge cells upregulate proton-pumping respiratory complexes (and downregulate ATP synthase) to support pH homeostasis.

    • DOI:10.1038/nrmicro2549 Krulwich et al. 2011: under acid challenge E. coli up-regulates proton-pumping respiratory complexes and down-regulates ATP synthase.
  • respiratory proton-pumping complexes enables baseline pH homeostasis RO:0002327

    Proton-pumping respiratory activity contributes to baseline pH homeostasis on the acidic side of the range.

    • DOI:10.1038/nrmicro2549 Krulwich et al. 2011: proton extrusion supports cytoplasmic pH maintenance under acid challenge.
  • alkaline challenge positively regulates cation/proton antiporters RO:0002213

    Under alkaline challenge cells activate cation/proton antiporters and F1Fo-ATP synthase proton-capture to support pH homeostasis.

    • DOI:10.1038/nrmicro2549 Krulwich et al. 2011: under alkaline stress cells activate inward proton transport via cation/proton antiporters and increase ATP synthase expression.

Provenance

Source
METPO (2025-11-25)
Definition source
DOI:10.1038/nrmicro2549

Parent traits (1)

Synonyms (4)

  • Alkali Tolerant EXACT_SYNONYM · metpo.owl
  • Facultative acidophile EXACT_SYNONYM · metpo.owl
  • Neutrophile EXACT_SYNONYM · metpo.owl
  • pHR_6_to_7 RELATED_SYNONYM · metpo.owl

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

  • METPO:1000461 [-1.688, -1.528, -1.234, +3.477, …]

512-dim DeepWalkSkipGramEnsmallen embedding from kg-microbe (2026-04-25).

Nearest neighbors in embedding space

Top-8 cosine-similar METPO traits from the 2026-04-25 deepwalk (512-D).

Deep research

Generated by just research-trait; source: research/traits/environment/ph_range_mid1-deep-research-falcon.md

Unreviewed literature output — not curated TraitMech content Ontology identifiers suggested below have not been resolved against their ontologies, and some are known to be wrong. Check any CURIE against the source before using it.
# Curation report: microbial pH range mid1

## Executive conclusion

**Target trait:** **“METPO:1000461”** (*pH range mid1*; ENVIRONMENT; CLASS; REVIEWED).

The safest interpretation is an **assay-observed capacity for growth across an external-pH interval of approximately 6–7**, characteristic of neutralophilic physiology. It should not be equated with an organism’s pH optimum, its complete growth range, or survival after transient acid/alkaline challenge. Neutralophiles as a broad physiological class may grow over approximately pH 5.5–9.0 while maintaining a much narrower cytoplasmic pH, historically estimated at about 7.5–7.7; a 2023 synthesis gives a more general internal-pH range of 7.0–7.5 for many cell types. At external pH near 7, *Escherichia coli* has a small inwardly alkaline ΔpH together with a substantial negative-inside membrane potential. (krulwich2011molecularaspectsof pages 1-3, poolman2023physicochemicalhomeostasisin pages 1-2)

The graph should therefore center on **near-neutral cytoplasmic pH, cytoplasmic buffering, proton-motive-force homeostasis, respiratory or ATPase-mediated proton transport, and cation/proton exchange**. NhaA, KefC, glutamate decarboxylase, and other named stress systems are valuable mechanistic examples, but most should not be represented as universal causes of the pH 6–7 growth phenotype.

## 1. Trait scope and boundaries

### Positive scope

The trait records growth support over an extracellular pH interval, ideally established from replicated growth curves or endpoint biomass/yield measurements in buffered media. The phenotype is environmentally conditional: temperature, medium composition, buffering species and capacity, ionic strength, oxygen availability, carbon source, inoculum history, and incubation time can all shift the observed limits.

A biologically plausible mechanistic interpretation is:

**external pH 6–7 → manageable proton activity at the cell surface → cytoplasmic buffering plus regulated proton/cation transport → near-neutral cytoplasmic pH and usable PMF → ATP synthesis, transport, enzyme function, and growth.**

PMF comprises ΔpH and electrical potential Δψ. Under standard conventions, bacterial interiors are usually alkaline and electrically negative relative to the exterior. Near external pH 7, ΔpH is small and Δψ supplies a substantial part of PMF. (krulwich2011molecularaspectsof pages 1-3, poolman2023physicochemicalhomeostasisin pages 1-2)

### Boundary cases

1. **pH optimum versus range:** growth optimal near pH 6.5 does not prove that the growth-supporting range spans 6–7.
2. **Growth versus survival:** enteric bacteria can survive nonpermissive gastric acidity and resume growth after return to neutral medium; that is acid resistance, not growth at the challenge pH. (krulwich2011molecularaspectsof pages 1-3)
3. **Broad neutralophile versus this bin:** the literature’s approximate pH 5.5–9.0 neutralophile range is broader than the ontology term’s specific 6–7 interval. (krulwich2011molecularaspectsof pages 1-3)
4. **Facultative acidophile and “alkali tolerant”:** these synonyms should be treated cautiously. Acidophilic growth or alkaline tolerance implies capacities beyond the core 6–7 phenotype and should not be inferred from this trait alone.
5. **Assay drift:** microbial metabolism can acidify or alkalinize weakly buffered media. Initial pH alone is therefore insufficient; final or continuous pH should be reported.
6. **Taxon-specific stress mechanisms:** GadB, NhaA, Ktr, and KefC evidence does not establish that every organism carrying this phenotype uses those systems.

## 2. Candidate nodes grouped by type

### Trait and environmental nodes

- **pH range mid1 — “METPO:1000461”**
- Parent trait — **METPO:1000332**
- External pH 6–7
- Hydrogen-ion activity / proton concentration
- Buffered growth medium
- Buffer capacity, temperature, ionic strength, salinity, oxygen availability, carbon source, and incubation time

### Chemicals and energetic quantities

- Proton — **CHEBI:15378**
- Sodium ion — **CHEBI:29101**
- Potassium ion — **CHEBI:29103**
- ATP — **CHEBI:15422**
- ADP — **CHEBI:16761**
- Proton motive force
- Transmembrane pH gradient, ΔpH
- Membrane potential, Δψ
- Inorganic and organic phosphates
- Glutamate and GABA, if an acid-stress subgraph is retained
- Glutathione and glutathione–electrophile adducts, if a KefC context subgraph is retained

### Cellular locations

- Cytoplasm — **GO:0005737**
- Plasma membrane — **GO:0005886**

Showing the first 60 of 192 lines of findings; the linked file also carries the run's front matter and the prompt it was given — read the full report.

Curation history

  1. · SEEDED_FROM_METPO · seed_from_metpo

    imported from data/raw/metpo.owl (CLASS)

  2. · CURATED_CAUSAL_GRAPH · claude

    Added DOI-backed definition and causal graph linking baseline pH-homeostasis at near-neutral external pH to the neutrophilic pH-range-mid1 bin.

  3. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002327×1, rdfs:subClassOf×1).

  4. · ENRICH_CAUSAL_GRAPH · claude

    Added 6 evidence-backed generic edges (6 new nodes) from the deep-research report.

  5. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002327×3).

  6. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0051453×1).

  7. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002213×2).

  8. · 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.

  9. · NORMALISE_NODE_TYPE · claude

    Normalised causal-node type(s) so one node_id means one thing corpus-wide (issue 356): proton_motive_force: BIOLOGICAL_PROCESS -> STATE. The schema's OWN example of STATE: 'a bioenergetic or molecular state of the cell (e.g. proton motive force ...) ... the state is the gradient / steady-value, not its establishment'. All 35 occurrences describe the gradient -- every description across all four types reads 'electrochemical proton gradient', including the 13 typed BIOLOGICAL_PROCESS ('Transmembrane electrochemical gradient generated by respiration'), which name the gradient and its provenance rather than the generating process. Nothing here means the establishment, so this is a retype and not a rename; records that DO mean the process already use a separate id (proton_motive_force_generation in ph_delta.yaml). Also settles the one edge #356 was filed for: phototrophic.yaml's CAPACITY typing was blocking `powers` (METPO:2007900), which is gated to BIOLOGICAL_PROCESS|STATE.