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human pathogen

METPO:1004004 · CLASS · REVIEWED

A pathogen that infects organisms of the species Homo sapiens.

Human-pathogen Homo sapiens host adaptation

DOI-backed graph linking human-adapted virulence factors, body-temperature and tissue tropism, and human-specific immune evasion to the human-pathogen phenotype.

Human-pathogen Homo sapiens host adaptation Interactive directed graph showing evidence-backed causal relationships for human pathogen.

Edge evidence

  • human-adapted virulence factors enables human tissue tropism RO:0002327

    Human-adapted virulence factors enable preferential adhesion and growth in human tissues.

    • DOI:10.1146/annurev.micro.62.081307.162938 virulence factors Supports virulence factors as enablers of human tissue tropism.
  • human tissue tropism enables human disease RO:0002327

    Tissue tropism supports establishment of human disease at specific anatomical sites.

    • DOI:10.1146/annurev.micro.62.081307.162938 virulence factors Supports tissue tropism as a determinant of human-disease pattern.
  • human immune evasion enables human disease RO:0002327

    Evasion of human immunity supports sustained infection and disease.

    • DOI:10.1038/nrmicro1592 secretion systems Supports secretion-system-delivered effectors in human immune evasion.
  • human disease manifests as human pathogen METPO:2007400

    Human disease manifests the human-pathogen trait.

    • DOI:10.1146/annurev.micro.62.081307.162938 virulence factors Supports the trait endpoint.
  • type IV secretion system enables host cell manipulation RO:0002327

    Type IV secretion systems translocate protein effectors and toxins that manipulate host cells during infection.

    • DOI:10.1038/s41579-023-00974-3 T4SSs function as protein effector translocators delivering effectors or toxins; viable targets to thwart infection by pathogens.
  • host cell manipulation enables human disease RO:0002327

    Effector-driven host cell manipulation supports establishment of human infection and disease.

    • DOI:10.1038/s41579-023-00974-3 Effector translocation enables host cell manipulation and infection by pathogens.
  • horizontal gene transfer enables acquisition of virulence/host-adaptation genes RO:0002327

    HGT via plasmids, transduction, transposons, and IS elements enables acquisition of virulence and host-adaptation genes.

    • DOI:10.1093/femsre/fuae019 HGT via conjugation, transduction, transposons, IS elements can be associated with gain of genes facilitating host tropism and virulence factors.
  • acquisition of virulence/host-adaptation genes contributes to human-adapted virulence factors RO:0002326

    Acquired genes contribute the human-adapted virulence factor repertoire underlying human pathogenicity.

    • DOI:10.1093/femsre/fuae019 Gene acquisition facilitates changes in host species tropism, including virulence factors enabling human-pathogenic lineages.
  • within-host genetic diversification enables within-host adaptation and chronic infection RO:0002327

    Hypermutation, structural variation, and MGE/phage insertions generate diversity driving within-host adaptation.

    • DOI:10.1146/annurev-pathmechdis-051122-111408 Secondary mechanisms including hypermutation, structural variation, and MGE/phage insertions can increase pathogenicity and facilitate long-term persistence.
  • within-host adaptation and chronic infection enables human disease RO:0002327

    Within-host adaptation increases pathogenicity and supports chronic human infection.

    • DOI:10.1146/annurev-pathmechdis-051122-111408 Within-host evolution can increase pathogenicity and facilitate long-term persistence in the host.
  • biofilm formation confers treatment resistance and persistence METPO:2007700

    Biofilm formation makes bacteria resistant to treatment and supports persistence.

    • DOI:10.3389/fmicb.2024.1370818 Bacteria can form biofilms, making them resistant to treatment.
  • treatment resistance and persistence enables human disease RO:0002327

    Treatment resistance and persistence exacerbate the severity and duration of human infection.

    • DOI:10.3389/fmicb.2024.1370818 Biofilm-associated resistance to treatment contributes to infection severity and persistence.

Provenance

Source
METPO (2025-11-25)
Definition source
DOI:10.1146/annurev.micro.62.081307.162938

Parent traits (1)

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

  • METPO:1004004 [-23.400, -36.820, -39.335, +4.843, …]

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/ecology/human_pathogen-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: **human pathogen** (METPO:1004004)

## Executive scope

**Recommended interpretation.** The trait denotes the demonstrated capacity of a microbial **strain or lineage** to establish infection in *Homo sapiens* (NCBITaxon:9606), including opportunistic infection where host state or barrier disruption is required. It is an ecological/host-range class, not a measure of disease severity. The graph endpoint should therefore be **capacity to infect a human host**, with upstream modules for access, colonization, nutrient acquisition, stress survival, immune evasion, replication, tissue damage, and dissemination.

Host association alone is insufficient. Human commensals may carry adhesins, capsules, secretion systems, siderophores, biofilm capacity, or antimicrobial-resistance genes without causing disease. Conversely, a pathogen need not encode every canonical virulence module. Pathogenicity is an emergent host–microbe property rather than an intrinsic consequence of one gene. Host tropism also ranges from human-restricted organisms to broad-host-range zoonoses; spillover into one person is distinct from adaptation that permits sustained human-to-human transmission. Barber and Fitzgerald emphasize that successful host switches require adaptation to distinct anatomy, physiology, immunity, and nutrient availability, and that pathogenicity-related mechanisms include colonization, nutrient acquisition, and immune evasion (barber2024mechanismsofhost pages 1-2).

**Nearby traits to keep separate**

- **Human-associated/commensal:** colonizes humans without demonstrated infection.
- **Pathobiont/opportunistic pathogen:** causes disease only under particular host, microbiome, barrier, or device conditions; still falls under human pathogen when infection is demonstrated, but should retain the qualifier.
- **Virulent:** severity or damage conditional on infection, not synonymous with ability to infect.
- **Zoonotic pathogen:** animal reservoir and transmission route; overlaps only when humans are infected.
- **Serum resistant, intracellular, toxigenic, biofilm forming, or antimicrobial resistant:** component phenotypes, neither individually necessary nor sufficient.
- **Genomically predicted pathogen:** hypothesis requiring phenotypic, epidemiological, or infection-model confirmation.

## Recommended causal architecture

A defensible graph should not use one universal linear chain. Use a convergent architecture:

**human exposure/barrier access → attachment or niche entry → nutrient acquisition + host-stress tolerance + immune evasion → survival/replication in a human niche → tissue invasion, damage, or dysfunction → human infection phenotype**.

Human specificity can enter at several points: adhesin–receptor compatibility, nutrient-receptor compatibility, toxin receptor recognition, or evasion of human complement and cell-autonomous immunity. Small sequence changes may alter these interactions: two substitutions in *Listeria monocytogenes* InlA can shift affinity toward murine E-cadherin, and nucleotide variation in *Salmonella* FimH is associated with host-specific serovars (barber2024mechanismsofhost pages 1-2).

## Candidate nodes by type

### Trait and organism nodes

| Candidate node | Suggested grounding | Curation note |
|---|---|---|
| human pathogen | METPO:1004004 | Graph endpoint |
| human host | NCBITaxon:9606 | Host taxon |
| interaction with host | GO:0044406 | Broad process; use more specific child terms where possible |
| pathogenesis | GO:0009405 | Useful intermediate process, not equivalent to endpoint |
| host colonization | Label-only unless a validated local ontology term is selected | Separate asymptomatic colonization from infection |
| dissemination in host | Label-only | Context-dependent |

### Environmental and experimental factors

- Human epithelial or mucosal surface; extracellular matrix; bloodstream; intracellular inclusion/vacuole.
- Wound, disrupted epithelial barrier, indwelling device, dysbiosis, immunocompromise, or elevated glucose: qualifying contexts rather than universal causes.
- Human serum; native serum contains active complement, whereas heat-inactivated serum is an experimental comparator.
- Nutritional immunity: sequestration of iron, zinc, and manganese by transferrin, lactoferrin, hemoglobin-associated pools, and calprotectin.
- Oxidative stress (GO:0006979), host temperature, acid stress, hypoxia, antimicrobial peptides, complement activation (GO:0006956), and immune response (GO:0006955).

### Genes, proteins, transporters, and complexes

- Adhesins: FimH; InlA/InlB; HopQ; Opa; UspA1; fibrinogen-binding proteins; SpsL.
- Host nutrient receptors: TbpA, TdfH, and IsdB.
- Siderophore machinery: enterobactin and EntE/EntF; generic siderophore biosynthesis/export/reuptake.
- Secretion systems and secreted effectors: T3SS and other taxon-specific systems; effectors should be represented individually when perturbation evidence exists.
- Complement-evasion factors: factor-H/C4BP-binding surface proteins, CspA, CHIPS, SCIN, and species-specific IgA proteases.
- Cell-autonomous immune-evasion factors: *Chlamydia trachomatis* GarD and *Shigella flexneri* IpaH7.8.
- Capsule/capsular polysaccharide; extracellular polymeric matrix and biofilm machinery.
- Stress/metabolic regulators: Hfq, ProQ, Skp, superoxide dismutases, isocitrate lyase, and malate synthase.
- Mobile genetic elements: plasmids, prophages, pathogenicity islands, and PICIs. Keep these as evolutionary carriers rather than direct universal causes.

### Chemicals and metabolites

Showing the first 60 of 211 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 causal graph linking human-adapted virulence factors, tissue tropism, immune evasion, and disease to the human-pathogen trait.

  3. · GROUND_CAUSAL_PREDICATES · claude

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

  4. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2007400×1).

  5. · RENAME_PREDICATE_LABELS · claude

    Renamed 2 causal-edge predicate label(s) to align with existing groundings: supports → enables ×2.

  6. · GROUND_CAUSAL_PREDICATES · claude

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

  7. · REMOVE_REDUNDANT_SYNONYM · claude

    Removed 1 synonym(s) whose text duplicated the label (seeder redundancy; no information lost).

  8. · ENRICH_CAUSAL_GRAPH · claude

    Added 8 evidence-backed generic edges (8 new nodes) from the deep-research report.

  9. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 8 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (RO:0002327×8).

  10. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0009292×1).

  11. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0042710×1).

  12. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0043684×1).

  13. · REGROUND_CAUSAL_EDGE · claude

    Re-grounded causal edge(s) off enables/RO:0002327 onto contributes to (RO:0002326), issue 334. biolink declares enables range 'biological process or activity', which only BIOLOGICAL_PROCESS, PATHWAY and MOLECULAR_FUNCTION satisfy, so an edge pointing at a GENE_OR_PROTEIN entailed a false type. The replacements are chosen per idiom rather than swept: a gene cluster ENCODES its product, a subunit is PART OF the complex it belongs to, and an energy source or acquired repertoire CONTRIBUTES TO the machine it powers or composes. All three declare no rdfs:domain or rdfs:range, so none can reintroduce the class of defect being removed.

  14. · REGROUND_CAUSAL_EDGE · claude

    Correction to the REGROUND_CAUSAL_EDGE event above, issue 334 review. That event enumerated three idioms and asserted that all three targets declare no rdfs:domain or rdfs:range. Two parts are now known to be wrong, though neither affects this record's own edge. The biolink:encodes half rested on a vacuous check - that term is absent from the pinned biolink model, tracked in issue 342. The "energy source ... the machine it powers" half was retracted: those four motive-force edges were reverted to enables and re-deferred, because biolink defines contributes to as contributing to the occurrence or GENERATION of the object, which a motive force does not do to a motor. This record's surviving edge, acquired genes contributing to the virulence factor repertoire, does fit that definition and is unchanged.

  15. · REGROUND_CAUSAL_EDGE · claude

    Edge biofilm_formation -> treatment_resistance_persistence in graph human_pathogen_anthropoid_adaptation: re-grounded it from enables/RO:0002327 to confers/METPO:2007700; retyped treatment_resistance_persistence to TRAIT. Issue 334. biolink declares enables range 'biological process or activity', which of CausalNodeTypeEnum only BIOLOGICAL_PROCESS, PATHWAY and MOLECULAR_FUNCTION satisfy, so this edge entailed a false type on its object. 'Tolerance to antimicrobial treatment and persistent infection' is a DISPOSITION -- what the organism would do under treatment -- not a quality it displays. Retyped to TRAIT, which makes this the same shape #302 solved for 164 edges, and `confers` already admits a BIOLOGICAL_PROCESS subject.