Abstract
Conidia of Aspergillus fumigatus are inhaled by humans on daily basis. As a consequence, these conidia can cause infections that differ in severity ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis. In this study we compared virulence of five A. fumigatus isolates in four different infection models to address the predictive value of different model systems. Two of the A. fumigatus strains were isolated from dogs with a non-invasive sino-nasal aspergillosis (DTO271-B5 and DTO303-F3), while three strains were isolated from human patients with invasive aspergillosis (Af293, ATCC46645 and CEA10). Infection models used encompassed cultured type II A549 lung epithelial cells, Protostelium aurantium amoeba, Galleria melonella larvae and zebrafish embryos. No major differences in virulence between these five strains were observed in the lung epithelial cell model. In contrast, strain ATCC46645 was most virulent in the amoeba and zebrafish model, whereas it was much less virulent in the Galleria infection model. DTO303-F3 was most virulent in the latter model. In general, reference strain Af293 was less virulent as compared to the other strains. Genome sequence analysis showed that this latter strain differed from the other four strains in 136 SNPs in virulence-related genes. Together, our results show that virulence of individual A. fumigatus strains show significant differences between infection models. We conclude that the predictive value of different model systems varies since the relative virulence across fungal strains does not hold up across different infection model systems.
Highlights
Aspergillus fumigatus is a saprotrophic fungus, feeding on dead or living organic matter [1]
Dormant conidia of A. fumigatus are surrounded by a protective layer of dihydroxynapthlene (DHN)-melanin and hydrophobin proteins which is shed during germination
As P. aurantium primarily recognizes swollen conidia of A. fumigatus, its phagocytic efficiency is highly dependent on the dynamics of the fungal germination process
Summary
Aspergillus fumigatus is a saprotrophic fungus, feeding on dead or living organic matter [1]. The 2–3 μm wide conidia [2] are dispersed via the air and hundreds of these conidia are inhaled by humans daily [3]. Upon inhalation, these conidia can cause lung infections that differ in severity. Allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA) and Aspergillus bronchitis are classified as non-invasive aspergillosis infections. Differences in virulence of Aspergillus fumigatus strains in four infection models marie-sklodowska-curie-actions https://www. Embo.org/funding-awards/fellowships/short-termfellowships.html The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Differences in virulence of Aspergillus fumigatus strains in four infection models marie-sklodowska-curie-actions https://www. embo.org/funding-awards/fellowships/short-termfellowships.html The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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