VAMPIROME

Vampire bat salivary proteins that modulate host hemostasis and immunity

Chris Mungall | AI-Assisted Gene Review

2026-06-22

Why this is interesting

  • Desmodus rotundus (vampire bat; UniProt code DESRO) feeds exclusively on blood.
  • To keep host blood flowing, its salivary glands secrete a cocktail of proteins that block coagulation, dissolve clots, dilate vessels, and dampen innate immunity.
  • These host-manipulating proteins are a rich source of anticoagulant and antithrombotic drug leads (e.g. the bat-derived plasminogen activator concept).
  • Yet most of the underlying gene products are poorly annotated in public databases.

Key biology: a blood-feeding pharmacopeia

The salivary secretome targets the host across several axes:

  • Hemostasis / coagulation — plasminogen activators, Kunitz/TFPI-like inhibitors, serpins, apyrase, phosphatase (platelet function).
  • Vascular tone / angiogenesis — natriuretic/CNP peptide, PACAP, ADAMTS metalloproteases.
  • Innate immune modulation — DNases (neutrophil function), chemokine/lymphotoxin-like cytokines, TSG-6-related TNF-inducible protein.
  • Antimicrobial defense — beta-defensin, lysozyme (accessory-gland enriched).

Source: Vampirome transcriptome/proteome of D. rotundus salivary glands (PMC3685427).

The approach: AI-assisted gene review

  • Curate DESRO salivary candidates within the AI gene review framework: synthesize literature, existing GO annotations, and bioinformatics into structured *-ai-review.yaml records.
  • Map Vampirome transcript IDs (BatTrinityAbyss-*, DrSigp-SigP-*) to TSA accessions (GABZ01*) and UniProt entries via NCBI E-utilities + UniProt REST.
  • Prioritize the most hemostasis/immune-relevant candidates for deep review.
  • Cross-links with the broader PARASITE_IMMUNE_MODULATORS project on host immune manipulation.

From transcript to UniProt: the mapping

Example mappings (transcript → TSA → UniProt → protein):

Transcript TSA UniProt Protein
BatTrinityAbyss-499018 GABZ01006477 K9IJK6 t-plasminogen activator
BatTrinityAbyss-541822 GABZ01007556 K9IZA2 Kunitz-type protease inhibitor 2
BatTrinityAbyss-532109 GABZ01002174 K9J287 Deoxyribonuclease-1-like 1
BatTrinityAbyss-506850 GABZ01008475 K9IFY6 C-C motif chemokine
BatTrinityAbyss-86412 GABZ01007969 K9IWR0 Lymphotoxin-alpha

Priority shortlist (13 candidates)

Focused on hemostasis and immune modulation:

  • Hemostasis: t-plasminogen activator (K9IJK6), Kunitz-type protease inhibitor 2 (K9IZA2), plasma protease C1 inhibitor (K9IYM3), ADAMTS-1 (K9IUF6)
  • Innate immune / neutrophil: Deoxyribonuclease-1-like 1 (K9J287), C-C motif chemokine (K9IFY6), Lymphotoxin-alpha (K9IWR0), TNF-inducible gene 6 / TSG-6 (K9IIP0)
  • Antimicrobial: Beta-defensin 1 (K9IFT7), lysozyme / LYZ (K9IWH5)
  • Vascular / other: Natriuretic peptides B (K9IWC0), SCP/CRISP (K9IWX5), Dipeptidyl peptidase 4 (K9J2R0)

Protein families represented

The secretome recruits recurring, repurposed protein families:

  • Protease inhibitors: Kunitz/TFPI-like, serpins (neuroserpin, alpha-1-antichymotrypsin, Serpin B6), cystatin, Kazal, TIL, alpha-macroglobulin, TIMP-like.
  • Proteases: plasminogen activator, ADAMTS metalloproteases, dipeptidyl peptidase 4.
  • Lipocalins: multiple putative salivary lipocalins (lipid/ligand binding).
  • CAP / antigen-5 (CRISP), chemokine/cytokine-like, DNases, antimicrobials (defensin, lysozyme).

A small number of families, repeatedly expanded, do the host-manipulation work.

Highlight: Draculin (seed gene)

  • Draculin — the canonical vampire bat anticoagulant, curated as Lactotransferrin (LTF), UniProt K9IMD0.
  • First seed gene with a completed annotation review in this project.
  • Anchors the project's hemostasis theme and serves as the template for reviewing the remaining secreted modulators.

Highlight: fibrinolytics & vasodilators

  • t-plasminogen activator (K9IJK6) — fibrinolytic; the family behind bat-derived plasminogen-activator therapeutics; keeps the wound site clot-free.
  • Natriuretic peptides B / CNP (K9IWC0) and PACAP (K9IGD6) — vasodilatory peptides that promote local blood flow.
  • vCGRP — a calcitonin gene-related peptide-like vasodilatory peptide reported in the literature (Toxins 2019, Kakumanu et al.); DESRO transcript/UniProt mapping still pending.

Challenges of curating these proteins

  • No Swiss-Prot entries for DESRO in this candidate set — every mapped entry is UniProtKB unreviewed (TrEMBL).
  • Names are frequently "Putative ..." and based on homology, not direct functional evidence.
  • Some Vampirome transcripts have no TSA/UniProt hit yet (e.g. several BatTrinityAbyss-* and DrSigp-SigP-* IDs; vCGRP unmapped).
  • Original condensed Table 4 / supplemental spreadsheets are on a moved NIAID portal and not yet re-accessible.
  • Function must be inferred carefully: salivary repurposing means the host-facing role can differ from the family's canonical role.

Status & future directions

Done:

  • Project structure, Table 4 extract, UniProt mapping, candidate list (Swiss-Prot prioritized — none found).
  • 13-candidate priority shortlist; UniProt/GOA fetched; falcon deep-research for all 13.
  • Annotation reviews + notes for Draculin and the full shortlist; core_functions for Draculin, K9IZA2, K9IYM3, K9J287.

Next:

  • Synthesize core functions across remaining candidates.
  • Map unmapped transcripts (incl. vCGRP/CALCA) and recover full supplemental tables.
  • Expand cross-links with PARASITE_IMMUNE_MODULATORS.

Thank you

A poorly-annotated, drug-relevant secretome — made curatable, one salivary protein at a time.

Project: projects/VAMPIROME.md | Code: DESRO (Desmodus rotundus)