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Updated: Oct 28, 2025
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
A new model for sensitive detection of zoonotic prions by PrP transgenic Drosophila
Alana M Thackray1, Olivier Andréoletti2, John Spiropoulos3
1Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Abstract:
Prions are transmissible protein pathogens most reliably detected by a bioassay in a suitable host, typically mice. However, the mouse bioassay is slow and cumbersome, and relatively insensitive to low titers of prion infectivity. Prions can be detected biochemically in vitro by the protein misfolding cyclic amplification (PMCA) technique, which amplifies disease-associated prion protein but does not detect bona fide prion infectivity. Here, we demonstrate that Drosophila transgenic for bovine prion protein (PrP) expression can serve as a model system for the detection of bovine prions significantly more efficiently than either the mouse prion bioassay or PMCA. Strikingly, bovine PrP transgenic Drosophila could detect bovine prion infectivity in the region of a 10-12 dilution of classical bovine spongiform encephalopathy (BSE) inoculum, which is 106-fold more sensitive than that achieved by the bovine PrP mouse bioassay. A similar level of sensitivity was observed in the detection of H-type and L-type atypical BSE and sheep-passaged BSE by bovine PrP transgenic Drosophila. Bioassays of bovine prions in Drosophila were performed within 7 weeks, whereas the mouse prion bioassay required at least a year to assess the same inoculum. In addition, bovine PrP transgenic Drosophila could detect classical BSE at a level 105-fold lower than that achieved by PMCA. These data show that PrP transgenic Drosophila represent a new tractable prion bioassay for the efficient and sensitive detection of mammalian prions, including those of known zoonotic potential.
Insights
Fruit flies expressing prion protein (PrP) offer a faster and more sensitive prion detection method. This novel Drosophila bioassay significantly outperforms traditional mouse models and PMCA for detecting bovine spongiform encephalopathy (BSE) prions.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Prions are protein-based infectious agents causing fatal neurodegenerative diseases.
- Current prion detection methods, like mouse bioassays and PMCA, are slow, labor-intensive, or lack sensitivity.
- Developing rapid, sensitive, and efficient prion detection systems is crucial for public health and diagnostics.
Purpose of the Study:
- To establish and validate a novel prion detection system using Drosophila melanogaster (fruit flies) engineered to express bovine prion protein (PrP).
- To compare the sensitivity and speed of this Drosophila-based prion bioassay against conventional mouse bioassays and protein misfolding cyclic amplification (PMCA).
Main Methods:
- Generation of transgenic Drosophila expressing bovine prion protein (PrP).
- Inoculation of transgenic Drosophila with various dilutions of bovine spongiform encephalopathy (BSE) prions.
- Comparison of detection limits and incubation times with bovine PrP transgenic mouse bioassays and PMCA.
Main Results:
- Transgenic Drosophila detected bovine prion infectivity at dilutions up to 10-12, representing a 106-fold increase in sensitivity compared to mouse bioassays.
- The Drosophila bioassay identified atypical and sheep-passaged BSE prions with high sensitivity.
- Prion detection in Drosophila was achieved within 7 weeks, significantly faster than the year-long mouse bioassay.
- Drosophila detected classical BSE at a 105-fold lower level than PMCA.
Conclusions:
- Prion protein transgenic Drosophila serve as a highly sensitive and efficient bioassay for detecting mammalian prions, including those with zoonotic potential.
- This novel Drosophila model offers a significant advancement over existing prion detection methods in terms of speed and sensitivity.
- Transgenic Drosophila represent a tractable and valuable tool for prion research and diagnostics.
