Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i>

Roles of the <i>Sec2p</i> Gene in the Growth and Pathogenicity Regulation of <i>Aspergillus fumigatus</i>

<i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) is a filamentous fungus that causes invasive aspergillosis in immunocompromised individuals. Regulating fungal growth is crucial for preventing disease development. This study found that deleting the guanine nucleotide exchan...

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Bibliographic Details
Main Authors: Yuhuan Liu, Shumi Shang, Cong Liu, Yichen Liu, Keyang Xu, Dan He, Li Wang
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Journal of Fungi
Subjects:
<i>Aspergillus fumigatus</i>
<i>Sec2p</i>
growth
autophagy
cell wall
virulence
Online Access:https://www.mdpi.com/2309-608X/11/1/36
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Summary:<i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) is a filamentous fungus that causes invasive aspergillosis in immunocompromised individuals. Regulating fungal growth is crucial for preventing disease development. This study found that deleting the guanine nucleotide exchange factor <i>Sec2p</i> gene led to slower <i>A. fumigatus</i> growth and reduced the fungal burden and mortality of infected mice. However, the mechanism by which this gene affects <i>A. fumigatus</i> growth and pathogenicity remains unclear. Transmission electron microscopy revealed that the vacuoles of the gene knockout strain <i>ΔSec2p</i> accumulated more autophagosomes, indicating inhibition of autophagosome degradation. When phenylmethylsulfonyl fluoride was applied to inhibit autophagosome degradation, the <i>ΔSec2p</i> strain produced fewer autophagosomes; the <i>ΔSec2p</i> autophagy pathway was inhibited, affecting <i>A. fumigatus</i>’ nutrient homeostasis and growth. Unlike the wild type, the <i>ΔSec2p</i> strain showed strong resistance to cell wall stress. When exposed to caspofungin, <i>Sec2p</i> negatively regulated the expression of cell wall integrity (CWI) pathway genes and participated in the cell wall stress response of <i>A. fumigatus</i>. Furthermore, this gene positively regulated the autophagy pathway and enhanced CWI pathway gene expression to respond to rapamycin-induced autophagy. In summary, <i>Sec2p</i> positively regulated the autophagy pathway; it negatively regulated the CWI pathway during cell wall stress, coordinating the growth and pathogenicity of <i>A. fumigatus</i>.
ISSN:2309-608X

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