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Detection of Invasive Pulmonary Aspergillosis in Haematological Malignancy Patients by using Lateral-flow Technology
Published on: March 22, 2012
Surface display of Gaussia princeps luciferase allows sensitive fungal pathogen detection during cutaneous
Stefanie Donat1, Mike Hasenberg, Tina Schäfer
1Institute of Molecular Infection Biology, Julius Maxilimilans University, Würzburg, Germany.
Abstract:
Non-invasive imaging techniques in microbial disease models have delivered valuable insights in the intimate pathogen-host interplay during infection. Here we describe evaluation and validation of a transgenic bioluminescence reporter strain of the human-pathogenic mold Aspergillus fumigatus, one of the main fungal pathogens affecting immunocompromised individuals. Expression and surface display of the Gaussia princeps luciferase allowed sensitive and rapid detection of luminescence emitted from this strain after substrate addition, with photon fluxes strongly correlating to the amounts of fungal conidia or germlings. The reporter strain allowed spatio-temporal monitoring of infection in a cutaneous model of aspergillosis, where neutropenic mice maintained the fungal burden while immunocompetent ones were able to clear it entirely. Most importantly, antifungal therapy could be followed in this type of disease model making use of the bioluminescent A. fumigatus strain. In conclusion, combining sensitivity of the Gaussia luciferase with a surface display expression system in the fungal host allows longitudinal infection studies on cutaneous forms of aspergillosis, providing perspective on drug screening approaches at high-throughput.
Insights
A new bioluminescent Aspergillus fumigatus strain allows sensitive, non-invasive tracking of fungal infections in real-time. This tool aids in studying infection dynamics and evaluating antifungal therapies in mouse models.
Area of Science:
- Mycology
- Infectious Diseases
- Biotechnology
Background:
- Non-invasive imaging is crucial for understanding pathogen-host interactions in microbial diseases.
- Aspergillus fumigatus is a significant fungal pathogen, particularly in immunocompromised individuals.
Purpose of the Study:
- To evaluate and validate a transgenic bioluminescence reporter strain of Aspergillus fumigatus.
- To enable sensitive, spatio-temporal monitoring of fungal infections and antifungal therapy.
Main Methods:
- Development of a transgenic Aspergillus fumigatus strain expressing Gaussia princeps luciferase.
- Utilizing bioluminescence detection for quantifying fungal burden in a cutaneous aspergillosis mouse model.
- Monitoring infection progression and response to antifungal treatment.
Main Results:
- The reporter strain exhibited sensitive and rapid luminescence detection, correlating with fungal conidia and germling amounts.
- Spatio-temporal monitoring of infection was achieved in both neutropenic and immunocompetent mice.
- The strain facilitated the tracking of antifungal therapy efficacy in the disease model.
Conclusions:
- The bioluminescent reporter strain enables longitudinal studies of cutaneous aspergillosis.
- This approach offers a sensitive tool for high-throughput drug screening and antifungal therapy evaluation.
