Diversity of hirudin and hirudin-like factor genes in the North-African medicinal leech, Hirudo troctina
Ahmed RB, Abilov A, Müller C (2024) · Parasitology Research · n=0
Study Profile
- Design
- molecular cloning and recombinant-expression analysis of 11 hirudin and hirudin-like factor (HLF) gene variants in the North-African medicinal leech Hirudo troctina (Tunisia, Germany collaboration; University of Tunis El Manar and University of Greifswald)
- Sample size (n)
- 0
- Intervention
- Identification and molecular cloning of 11 hirudin/HLF variant genes from H. troctina; recombinant expression and purification of representative putative hirudin variants and HLFs followed by functional characterization for thrombin-inhibiting potencies
- Comparator
- Cross-species comparison with European Hirudo, Hirudinaria, and Whitmania hirudin/HLF gene sequences
- Primary endpoint
- Number and structural diversity of hirudin and HLF genes in H. troctina; thrombin-inhibitory activity of recombinant variants; phylogenetic placement of H. troctina factors
- Primary result
- Identified 11 hirudin/HLF variant genes in H. troctina - the highest diversity among European Hirudo species; three genes show recombination of exons/introns from different archetype genes; recombinant putative hirudin variants and HLF representatives showed measurable thrombin-inhibitory activity; phylogenetic analyses support early divergence of hirudins and HLFs in leech evolution
- Follow-up duration
- not applicable (gene-cloning and recombinant-protein mechanism study)
- PMID
- 39540973
Key Findings
- H. troctina genome contains 11 hirudin/HLF variant genes - the largest reported diversity among European Hirudo species
- Three of the 11 genes appear to result from recombination of exons and introns from distinct archetype genes
- Recombinant putative hirudin and HLF variants from H. troctina show measurable thrombin-inhibitory activity
- Phylogenetic analyses support early divergence of hirudins and HLFs from a common ancestral gene
- Adds North-African (Tunisian) medicinal leech data to the predominantly European-and-Asian molecular leech pharmacology base
Limitations
- Mechanistic gene-cloning and recombinant-protein study only - no human or animal clinical outcomes
- Thrombin-inhibition potencies characterized in vitro - in vivo bioavailability and clinical efficacy not assessed
- Functional characterization limited to selected representative variants, not all 11 genes
- Limited information on the natural expression levels and salivary release dynamics of each variant
- Geographic scope limited to North Africa - generalizability of H. troctina pharmacology untested clinically
Clinical Implications
Ahmed 2024 expands the molecular pharmacology landscape of medicinal leeches by documenting that H. troctina contains an unusually rich repertoire of hirudin and hirudin-like factor (HLF) variant genes. For ASH editorial purposes, the trial supports the broader case that leech salivary pharmacology is highly diversified across geography and species, and motivates future research on H. troctina-derived therapeutics. The trial does not change clinical practice in the US (where Hirudo verbana is the principal commercial species) but does add mechanistic context for compound-registry pages on hirudin and related factors.
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