The Aspergillus fumigatus maiA gene contributes to cell wall homeostasis and fungal virulence

In this study, two distinct infection models of , using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated uncovered 140 fungal genes up-regulated in commo...

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Published inFrontiers in cellular and infection microbiology Vol. 14; p. 1327299
Main Authors Guruceaga, Xabier, Perez-Cuesta, Uxue, Martin-Vicente, Adela, Pelegri-Martinez, Eduardo, Thorn, Harrison I, Cendon-Sanchez, Saioa, Xie, Jinhong, Nywening, Ashley V, Ramirez-Garcia, Andoni, Fortwendel, Jarrod R, Rementeria, Aitor
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 2024
Subjects
Animals
Aspergillus fumigatus
cell wall
Cell Wall - metabolism
Fungal Proteins - genetics
Fungal Proteins - metabolism
Homeostasis
Humans
maiA
Mice
microarray
virulence
Virulence - genetics
microarray
virulence
Aspergillus fumigatus
cell wall
maiA
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Summary:In this study, two distinct infection models of , using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubated uncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously published transcriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, the gene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption of resulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of β-glucans within the cell wall but did not show lack of chitin or mannans. The mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking the gene to fungal cell wall homeostasis and virulence.
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ISSN:2235-2988
2235-2988
DOI:10.3389/fcimb.2024.1327299