pH delta mid1

METPO:1000475 · CLASS · REVIEWED

A pH delta phenotype with a growth-supporting pH breadth of approximately 2–3 pH units, characteristic of organisms with moderate pH-tolerance breadth.

pH-delta-mid1 moderate-breadth pH homeostasis

DOI-backed graph linking moderate pH-homeostasis flexibility to a pH growth breadth of approximately 2–3 pH units.

Edge evidence

moderate pH-homeostasis flexibility confers pH delta mid1 METPO:2007700
Moderate pH-homeostasis flexibility yields a 2–3 pH-unit pH-delta breadth.
- DOI:10.1038/nrmicro2549 pH homeostasis Supports moderate flexibility as the basis of an intermediate breadth.
pH delta mid1 is a pH delta rdfs:subClassOf
pH delta mid1 is a quantitative bin of the pH-delta phenotype.
- DOI:10.1038/nrmicro2549 external pH Supports the 2–3 unit breadth as a value within the pH-delta distribution.
F0F1-ATPase contributes to cytoplasmic pH homeostasis RO:0002326
Under acid stress F0F1-ATPase hydrolyzes ATP to consume/export intracellular H+, maintaining cytoplasmic pH.
- DOI:10.3390/microorganisms12091774 F0F1-ATPase under acid stress hydrolyzes ATP to consume intracellular H+ to maintain homeostasis; broad pH-homeostasis mechanism.
glutamine/glutamate decarboxylation pathway consumes intracellular proton (H+) biolink:consumes
Coupled glutamine conversion and glutamate decarboxylation consume two intracellular H+, enhancing acid resistance.
- DOI:10.3390/microorganisms12091774 Glutamine conversion and glutamate decarboxylation can act together to consume two H+; pathway-level proton-consumption module.
YbaS glutaminase produces ammonia METPO:2007800
YbaS glutaminase converts glutamine to glutamate and releases ammonia, which neutralizes intracellular protons.
- DOI:10.3390/microorganisms12091774 The glutaminase YbaS converts glutamine to glutamate and releases ammonia, which neutralizes intracellular protons.
membrane saturated fatty acid content decreases proton diffusion across membrane RO:0002212
A higher proportion of saturated membrane fatty acids limits passive proton diffusion across the membrane.
- DOI:10.1128/aem.00569-24 Conversion of unsaturated to saturated fatty acids limits proton diffusion; broadly plausible membrane-permeability mechanism.
oxidative phosphorylation / electron transport chain maintains proton motive force
Upregulated oxidative phosphorylation/ETC increases proton export and maintains the proton motive force, helping resist cytoplasmic pH decreases.
- DOI:10.3390/microorganisms12081565 Upregulation of oxidative phosphorylation genes increases proton export rate and maintains a proton motive force that helps cells resist cytoplasmic pH decreases under mild acid (pH 6.0) growth.
proton motive force contributes to cytoplasmic pH homeostasis RO:0002326
A maintained proton motive force supports cytoplasmic pH homeostasis under acid stress.
- DOI:10.3390/microorganisms12081565 PMF generated/maintained by oxidative phosphorylation helps cells resist cytoplasmic pH decreases.
cytoplasmic pH homeostasis contributes to moderate pH-homeostasis flexibility RO:0002326
Cytoplasmic pH homeostasis modules collectively underlie moderate pH-homeostasis flexibility.
- DOI:10.3390/microorganisms12091774 Proton-consumption and proton-export modules maintaining cytoplasmic pH underpin homeostatic flexibility across a few pH units.

Provenance

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

Parent traits (1)

pH delta METPO:1000232

Synonyms (1)

pHd_2_3 RELATED_SYNONYM · metpo.owl

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

METPO:1000475 [-0.998, -0.536, -1.733, +2.157, …]

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).

environment pH range mid1 0.741
environment pH range mid2 0.738
environment pH range low 0.737
environment pH range mid3 0.673
environment temperature delta mid2 0.673
environment temperature range mid1 0.658
environment temperature range low 0.657
environment pH optimum mid2 0.626

Deep research

Generated by just research-trait; source: research/traits/environment/ph_delta_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.

# Microbial Trait Causal Graph Research Report

## Target Trait: pH delta mid1 (METPO:1000475)

**Trait identifier:** METPO:1000475  
**Trait category:** ENVIRONMENT  
**Trait label:** pH delta mid1  
**Definition:** A pH delta phenotype with a growth-supporting pH breadth of approximately 2–3 pH units, characteristic of organisms with moderate pH-tolerance breadth.  
**Parent trait:** METPO:1000232

---

## 1. Trait Scope and Boundaries

METPO:1000475 represents an assay-observed **growth-supporting pH breadth** spanning approximately 2–3 pH units under defined cultivation conditions. It is operationally distinct from: (a) optimum pH (the single best pH value), (b) transient acid or alkali survival or shock tolerance measured over short exposures, (c) pH preference derived purely from field-survey distribution data, and (d) active pH modification by excretion of acids or bases that changes external pH during growth (sanchezclemente2020carbonsourceinfluence pages 14-16, sanchezclemente2020carbonsourceinfluence pages 1-3). The trait focuses on the range of **initial external pH values** across which reproducible vegetative growth can be sustained, reflecting an integrated physiological capacity to maintain intracellular homeostasis and structural integrity in moderately variable pH environments (krulwich2011molecularaspectsof pages 5-6).

Several experimental factors confound observed breadth: buffering capacity of medium, carbon source identity, and accumulation of metabolic end-products during growth can shift extracellular pH substantially and irreversibly. For example, *E. coli* grown on glucose in minimal medium showed a sudden pH drop during exponential growth that, if extracellular pH fell below 6, became irreversible and arrested further growth, whereas citrate or other oxidized carbon sources led to net alkalinization (sanchezclemente2020carbonsourceinfluence pages 1-3). Thus, the measured breadth is both an intrinsic microbial trait and assay-dependent (sanchezclemente2020carbonsourceinfluence pages 14-16).

---

## 2. Candidate Causal Graph Entities

Below are grouped candidate entities identified through literature review (2023–2024 recent sources plus foundational studies). Ontology CURIEs are provided where stable generic identifiers were verified; label-only entries are shown where species-specific or function-family identifiers were ambiguous.

### Environmental factors and assay parameters
- External pH (ENVO:3100033 or label; also recorded as pHe or pH_external)
- Medium buffering capacity (assay parameter, label-only)
- Carbon source identity (label-only; examples: glucose, citrate, glycerol, fumarate)
- Organic acid accumulation (label-only or CHEBI as specific compounds)

### Cellular biophysical quantities
- Intracellular pH / cytoplasmic pH (GO:0006885 regulation of intracellular pH; also pHi)
- Proton motive force (PMF; label-only or GO:0015986 proton-transporting ATP synthase activity related)
- Membrane potential / transmembrane electrical potential (ψ; label-only)
- Osmotic pressure (label-only)

### Chemical species
- Proton (CHEBI:15378)
- Hydroxide ion (CHEBI:16234)
- Sodium ion (CHEBI:29101)
- Potassium ion (CHEBI:29103)
- Chloride ion (CHEBI:17996)
- Glutamate (CHEBI:29985)
- GABA / γ-aminobutyric acid (CHEBI:16865)
- Arginine (CHEBI:29016)
- Agmatine (CHEBI:17431)
- Calcium ion (CHEBI:29108)
- Magnesium ion (CHEBI:18420)

### Proteins, enzymes, complexes, and transporters

**Proton pumps:**
- F1Fo ATPase (proton-translocating ATPase; EC:7.1.2.2; label for family or organism-specific UniProt entries)
- V-type H+-ATPase (vacuolar in eukaryotes; bacterial homologs; label-only in bacteria)
- H+-PPase (membrane pyrophosphatase; label or Rhea/EC)

**Proton-ion antiporters:**
- NhaA (Na+/H+ antiporter; label; in *E. coli* stoichiometry ~2H+/1Na+)
- NhaB (Na+/H+ antiporter; label)
- ClcA (Cl–/H+ antiporter; label)

Showing the first 60 of 375 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

2026-05-05T01:35:46.838958+00:00 · SEEDED_FROM_METPO · seed_from_metpo
imported from data/raw/metpo.owl (CLASS)
2026-05-13T10:00:00-07:00 · CURATED_CAUSAL_GRAPH · claude
Added DOI-backed definition and causal graph linking moderate pH-homeostasis flexibility to the moderate-breadth pH-delta-mid1 bin.
2026-05-20T03:35:30Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000202×1, rdfs:subClassOf×1).
2026-06-23T00:00:00Z · ENRICH_CAUSAL_GRAPH · claude
Added 7 evidence-backed generic edges (10 new nodes) from the deep-research report.
2026-06-24T17:21:10Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 6 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002326×3, biolink:consumes×1, METPO:2000202×1, RO:0002212×1).
2026-06-24T17:21:17Z · GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0051453×1, CHEBI:16134×1).
2026-08-06T01:00:00Z · MIGRATE_MICROBE_DOMAIN_EDGES · claude
Re-grounded 1 causal edge(s) off microbe-domain METPO predicates (1 to confers), issue 301. The previous predicates are transitively rdfs:subPropertyOf METPO:2000001, whose rdfs:domain is METPO:1000525 (microbe), so a causal-graph subject entailed that the subject IS a microbe; CausalNodeTypeEnum has no organism member, so no such edge could ever satisfy the domain. Edge directions are unchanged - this pass only relabels and re-grounds. RO:0002234 (has output) is used where the subject is an activity, since biolink gives it the domain 'biological process or activity'; the METPO replacements are proposed in proposals/metpo_traitmech_v8 and v9 and are placeholder ids until METPO mints them.
2026-08-06T02:00:00Z · MIGRATE_MICROBE_DOMAIN_EDGES_PART2 · claude
Re-grounded 1 causal edge(s) off microbe-domain METPO predicates onto their causal-graph counterparts (1 to produces), issue 301 part 2. The previous predicates are transitively rdfs:subPropertyOf METPO:2000001, whose rdfs:domain is METPO:1000525 (microbe), so a causal-graph subject entailed that the subject IS a microbe; CausalNodeTypeEnum has no organism member, so no such edge could ever satisfy the domain. Each replacement is a 1:1 mirror of its source predicate that changes only the domain, so the claim each edge makes is unchanged and directions are unchanged. The replacements are proposed in proposals/metpo_traitmech_v9 and are placeholder ids until METPO mints them.
2026-08-15T02:00:00Z · 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.
2026-08-16T02:00:00Z · NORMALISE_NODE_TYPE · claude
Under the PATHWAY-vs-BIOLOGICAL_PROCESS rule, one node_id means one thing corpus-wide (issue 356): oxidative_phosphorylation is typed PATHWAY. PATHWAY is a named, conventionally enumerable multi-step route; BIOLOGICAL_PROCESS is everything else. A named route through enumerable complexes -- environment/ph_delta_mid1.yaml lists them (nuo, cyo, ndh, sdh). The rule breaks what was a 2-2 tie before this tranche.