Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions
ABSTRACTCryptococcus neoformans is an environmental yeast that primarily affects immunocompromised individuals, causing respiratory infections and life-threatening meningoencephalitis. Treatment is complicated by limited antifungal options, with concerns such as adverse effects, dose-limiting toxici...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2024.2327883 |
| _version_ | 1797263212059557888 |
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| author | Eliane Vanhoffelen Lori Vermoesen Lauren Michiels Katrien Lagrou Agustin Reséndiz-Sharpe Greetje Vande Velde |
| author_facet | Eliane Vanhoffelen Lori Vermoesen Lauren Michiels Katrien Lagrou Agustin Reséndiz-Sharpe Greetje Vande Velde |
| author_sort | Eliane Vanhoffelen |
| collection | DOAJ |
| description | ABSTRACTCryptococcus neoformans is an environmental yeast that primarily affects immunocompromised individuals, causing respiratory infections and life-threatening meningoencephalitis. Treatment is complicated by limited antifungal options, with concerns such as adverse effects, dose-limiting toxicity, blood–brain barrier permeability, and resistance development, emphasizing the critical need to optimize and expand current treatment options against invasive cryptococcosis. Galleria mellonella larvae have been introduced as an ethical intermediate for in vivo testing, bridging the gap between in vitro antifungal screening and mouse studies. However, current infection readouts in G. mellonella are indirect, insensitive, or invasive, which hampers the full potential of the model. To address the absence of a reliable non-invasive method for tracking infection, we longitudinally quantified the cryptococcal burden in G. mellonella using bioluminescence imaging (BLI). After infection with firefly luciferase-expressing C. neoformans, the resulting bioluminescence signal was quantitatively validated using colony-forming unit analysis. Longitudinal comparison of BLI to health and survival analysis revealed increased sensitivity of BLI in discriminating cryptococcal burden during early infection. Furthermore, BLI improved the detection of treatment efficacy using first-line antifungals, thereby benchmarking this model for antifungal testing. In conclusion, we introduced BLI as a real-time, quantitative readout of cryptococcal burden in G. mellonella over time, enabling more sensitive and reliable antifungal screening. |
| first_indexed | 2024-04-25T00:09:25Z |
| format | Article |
| id | doaj.art-b610f3738b4c4b41b80c060fe02c5b10 |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-04-25T00:09:25Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-b610f3738b4c4b41b80c060fe02c5b102024-03-13T15:36:02ZengTaylor & Francis GroupVirulence2150-55942150-56082024-12-0115110.1080/21505594.2024.2327883Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditionsEliane Vanhoffelen0Lori Vermoesen1Lauren Michiels2Katrien Lagrou3Agustin Reséndiz-Sharpe4Greetje Vande Velde5Department of Imaging and Pathology, Biomedical MRI unit/MoSAIC, KU Leuven, Leuven, BelgiumDepartment of Imaging and Pathology, Biomedical MRI unit/MoSAIC, KU Leuven, Leuven, BelgiumDepartment of Imaging and Pathology, Biomedical MRI unit/MoSAIC, KU Leuven, Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, BelgiumDepartment of Imaging and Pathology, Biomedical MRI unit/MoSAIC, KU Leuven, Leuven, BelgiumDepartment of Imaging and Pathology, Biomedical MRI unit/MoSAIC, KU Leuven, Leuven, BelgiumABSTRACTCryptococcus neoformans is an environmental yeast that primarily affects immunocompromised individuals, causing respiratory infections and life-threatening meningoencephalitis. Treatment is complicated by limited antifungal options, with concerns such as adverse effects, dose-limiting toxicity, blood–brain barrier permeability, and resistance development, emphasizing the critical need to optimize and expand current treatment options against invasive cryptococcosis. Galleria mellonella larvae have been introduced as an ethical intermediate for in vivo testing, bridging the gap between in vitro antifungal screening and mouse studies. However, current infection readouts in G. mellonella are indirect, insensitive, or invasive, which hampers the full potential of the model. To address the absence of a reliable non-invasive method for tracking infection, we longitudinally quantified the cryptococcal burden in G. mellonella using bioluminescence imaging (BLI). After infection with firefly luciferase-expressing C. neoformans, the resulting bioluminescence signal was quantitatively validated using colony-forming unit analysis. Longitudinal comparison of BLI to health and survival analysis revealed increased sensitivity of BLI in discriminating cryptococcal burden during early infection. Furthermore, BLI improved the detection of treatment efficacy using first-line antifungals, thereby benchmarking this model for antifungal testing. In conclusion, we introduced BLI as a real-time, quantitative readout of cryptococcal burden in G. mellonella over time, enabling more sensitive and reliable antifungal screening.https://www.tandfonline.com/doi/10.1080/21505594.2024.2327883Galleria mellonellacryptococcus neoformansantifungal screeningbioluminescence imagingcryptococcosisfungal infection |
| spellingShingle | Eliane Vanhoffelen Lori Vermoesen Lauren Michiels Katrien Lagrou Agustin Reséndiz-Sharpe Greetje Vande Velde Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions Virulence Galleria mellonella cryptococcus neoformans antifungal screening bioluminescence imaging cryptococcosis fungal infection |
| title | Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions |
| title_full | Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions |
| title_fullStr | Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions |
| title_full_unstemmed | Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions |
| title_short | Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions |
| title_sort | sensitive bioluminescence imaging of cryptococcosis in galleria mellonella improves antifungal screening under in vivo conditions |
| topic | Galleria mellonella cryptococcus neoformans antifungal screening bioluminescence imaging cryptococcosis fungal infection |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2024.2327883 |
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