Longitudinal multimodal imaging-compatible mouse model of triazole-sensitive and -resistant invasive pulmonary aspergillosis
dc.contributor.author | Resendiz-Sharpe, A | |
dc.contributor.author | da Silva, RP | |
dc.contributor.author | Geib, E | |
dc.contributor.author | Vanderbeke, L | |
dc.contributor.author | Seldeslachts, L | |
dc.contributor.author | Hupko, C | |
dc.contributor.author | Brock, M | |
dc.contributor.author | Lagrou, K | |
dc.contributor.author | Vande Velde, G | |
dc.date.accessioned | 2022-07-07T12:11:31Z | |
dc.date.issued | 2022-03-30 | |
dc.date.updated | 2022-07-07T10:20:23Z | |
dc.description.abstract | Invasive pulmonary aspergillosis (IPA) caused by the mold Aspergillus fumigatus is one of the most important life-threatening infections in immunocompromised patients. The alarming increase of isolates resistant to the first-line recommended antifungal therapy urges more insights into triazole-resistant A. fumigatus infections. In this study, we systematically optimized a longitudinal multimodal imaging-compatible neutropenic mouse model of IPA. Reproducible rates of pulmonary infection were achieved through immunosuppression (sustained neutropenia) with 150 mg/kg cyclophosphamide at day -4, -1 and 2, and an orotracheal inoculation route in both sexes. Furthermore, increased sensitivity of in vivo bioluminescence imaging for fungal burden detection, as early as the day after infection, was achieved by optimizing luciferin dosing and through engineering isogenic red-shifted bioluminescent A. fumigatus strains, one wild type and two triazole-resistant mutants. We successfully tested appropriate and inappropriate antifungal treatment scenarios in vivo with our optimized multimodal imaging strategy, according to the in vitro susceptibility of our luminescent fungal strains. Therefore, we provide novel essential mouse models with sensitive imaging tools for investigating IPA development and therapy in triazole-susceptible and triazole-resistant scenarios. | en_GB |
dc.description.sponsorship | Fonds Wetenschappelijk Onderzoek (FWO) | en_GB |
dc.description.sponsorship | KU Leuven | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | University of Nottingham | en_GB |
dc.format.extent | dmm049165- | |
dc.format.medium | Print-Electronic | |
dc.identifier.citation | Vol. 15(3), article dmm049165 | en_GB |
dc.identifier.doi | https://doi.org/10.1242/dmm.049165 | |
dc.identifier.grantnumber | 1506114N | en_GB |
dc.identifier.grantnumber | G057721N | en_GB |
dc.identifier.grantnumber | C24/17/061 | en_GB |
dc.identifier.grantnumber | STG/15/024 | en_GB |
dc.identifier.grantnumber | 11E9819N | en_GB |
dc.identifier.grantnumber | 1186121N | en_GB |
dc.identifier.grantnumber | MR/N017528/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/130179 | |
dc.language.iso | en | en_GB |
dc.publisher | The Company of Biologists | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/35352801 | en_GB |
dc.rights | © 2022. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. | en_GB |
dc.subject | Antifungal resistance | en_GB |
dc.subject | Bioluminescence imaging | en_GB |
dc.subject | Invasive bronchopulmonary aspergillosis | en_GB |
dc.subject | Micro-CT | en_GB |
dc.subject | Murine model | en_GB |
dc.title | Longitudinal multimodal imaging-compatible mouse model of triazole-sensitive and -resistant invasive pulmonary aspergillosis | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-07-07T12:11:31Z | |
dc.identifier.issn | 1754-8403 | |
exeter.article-number | ARTN dmm049165 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from the Company of Biologists via the DOI in this record | en_GB |
dc.description | Data availability: Codon-optimized, red-shifted thermostable firefly luciferase sequence: lucOPT_red_TS, GenScript; GenBank accession number: MT554554. | en_GB |
dc.identifier.eissn | 1754-8411 | |
dc.identifier.journal | Disease Models and Mechanisms | en_GB |
dc.relation.ispartof | Dis Model Mech, 15(3) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | en_GB |
dcterms.dateAccepted | 2022-01-09 | |
dc.rights.license | CC BY | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2022-03-30 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-07-07T12:06:28Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2022-07-07T12:12:02Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2022-03-30 |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © 2022. Published by The Company of Biologists Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.