Prolonged Subculturing of Aspergillus fumigatus on Galleria Extract Agar Results in Altered Virulence and Sensitivity to Antifungal Agents

Aspergillus fumigatus is an environmental saprophyte and opportunistic fungal pathogen of humans. The aim of the work presented here was to examine the effect of serially subculturing A. fumigatus on agar generated from Galleria mellonella larvae in order to characterize the alterations in the pheno...

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Published in:Cells (Basel, Switzerland) Vol. 12; no. 7; p. 1065
Main Authors: Curtis, Aaron, Walshe, Kieran, Kavanagh, Kevin
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 31.03.2023
MDPI
Subjects:
Agar - pharmacology
Amphotericin B
Animals
Antifungal agents
Antifungal Agents - pharmacology
Aspergillus
Aspergillus fumigatus
Cystic fibrosis
Galleria
Genomes
Hemocytes
Histone H2A
Humans
Hydrogen peroxide
Immune response
immunity
Immunological tolerance
infection
Itraconazole
Kinases
Larva
mini-model
Moths
Opportunist infection
Oxidative stress
passaging
Pathogens
Phenotypes
Plant Extracts - pharmacology
Proteomics
Statistical analysis
Virulence
St Louis Missouri
United Kingdom > UK
United States > US
Aspergillus
infection
Galleria
virulence
mini-model
passaging
immunity
ISSN:2073-4409, 2073-4409
Online Access:Get full text
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Summary:Aspergillus fumigatus is an environmental saprophyte and opportunistic fungal pathogen of humans. The aim of the work presented here was to examine the effect of serially subculturing A. fumigatus on agar generated from Galleria mellonella larvae in order to characterize the alterations in the phenotypes that might occur. The passaged strains showed alterations in virulence, antifungal susceptibility, and in protein abundances that may indicate adaptation after 25 passages over 231 days on Galleria extract agar. Passaged strains demonstrated reduced virulence in G. mellonella larvae and increased tolerance to hemocyte-mediated killing, hydrogen peroxide, itraconazole, and amphotericin B. A label-free proteomic analysis of control and passaged A. fumigatus strains revealed a total of 3329 proteins, of which 1902 remained following filtration, and 32 proteins were statistically significant as well as differentially abundant. Proteins involved in the response to oxidative stress were altered in abundance in the passaged strain and included (S)-S-oxide reductase (+2.63-fold), developmental regulator FlbA (+2.27-fold), and histone H2A.Z (−1.82-fold). These results indicate that the prolonged subculturing of A. fumigatus on Galleria extract agar results in alterations in the susceptibility to antifungal agents and in the abundance of proteins associated with the oxidative stress response. The phenomenon may be a result of selection for survival in adverse conditions and highlight how A. fumigatus may adapt to tolerate the pulmonary immune response in cases of human infection.
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ISSN:2073-4409
2073-4409
DOI:10.3390/cells12071065