The impact of episporic modification of Lichtheimia corymbifera on virulence and interaction with phagocytes
Please always quote using this URN: urn:nbn:de:bvb:20-opus-352506
- Fungal infections caused by the ancient lineage Mucorales are emerging and increasingly reported in humans. Comprehensive surveys on promising attributes from a multitude of possible virulence factors are limited and so far, focused on Mucor and Rhizopus. This study addresses a systematic approach to monitor phagocytosis after physical and enzymatic modification of the outer spore wall of Lichtheimia corymbifera, one of the major causative agents of mucormycosis. Episporic modifications were performed and their consequences on phagocytosis,Fungal infections caused by the ancient lineage Mucorales are emerging and increasingly reported in humans. Comprehensive surveys on promising attributes from a multitude of possible virulence factors are limited and so far, focused on Mucor and Rhizopus. This study addresses a systematic approach to monitor phagocytosis after physical and enzymatic modification of the outer spore wall of Lichtheimia corymbifera, one of the major causative agents of mucormycosis. Episporic modifications were performed and their consequences on phagocytosis, intracellular survival and virulence by murine alveolar macrophages and in an invertebrate infection model were elucidated. While depletion of lipids did not affect the phagocytosis of both strains, delipidation led to attenuation of LCA strain but appears to be dispensable for infection with LCV strain in the settings used in this study. Combined glucano-proteolytic treatment was necessary to achieve a significant decrease of virulence of the LCV strain in Galleria mellonella during maintenance of the full potential for spore germination as shown by a novel automated germination assay. Proteolytic and glucanolytic treatments largely increased phagocytosis compared to alive resting and swollen spores. Whilst resting spores barely (1–2%) fuse to lysosomes after invagination in to phagosomes, spore trypsinization led to a 10-fold increase of phagolysosomal fusion as measured by intracellular acidification. This is the first report of a polyphasic measurement of the consequences of episporic modification of a mucormycotic pathogen in spore germination, spore surface ultrastructure, phagocytosis, stimulation of Toll-like receptors (TLRs), phagolysosomal fusion and intracellular acidification, apoptosis, generation of reactive oxygen species (ROS) and virulence.…
Author: | Mohamed I. Abdelwahab Hassan, Monique Keller, Michael Hillger, Ulrike Binder, Stefanie Reuter, Kristina Herold, Anusha Telagathoti, Hans-Martin Dahse, Saiedeh Wicht, Nora Trinks, Sandor Nietzsche, Tanja Deckert-Gaudig, Volker Deckert, Ralf Mrowka, Ulrich Terpitz, Hans Peter Saluz, Kerstin Voigt |
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URN: | urn:nbn:de:bvb:20-opus-352506 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Language: | English |
Parent Title (English): | Computational and Structural Biotechnology Journal |
Year of Completion: | 2021 |
Volume: | 19 |
Pagenumber: | 880-896 |
Source: | Computational and Structural Biotechnology Journal (2021) 19:880-896. https://doi.org/10.1016/j.csbj.2021.01.023 |
DOI: | https://doi.org/10.1016/j.csbj.2021.01.023 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Tag: | Galleria mellonella; atomic force microscopy (AFM); hyperspectral imaging (HIS); intracellular survival; monocytes; transmission electron microscopy (TEM) |
Release Date: | 2024/11/28 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |