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Roles of the Sec2p Gene in the Growth and Pathogenicity Regulation of Aspergillus fumigatus

Summary

Researchers studied a specific gene called Sec2p in a dangerous fungus that causes serious lung infections in people with weak immune systems. By removing this gene, they found the fungus grew much slower, was less deadly to mice, and the infected animals survived longer. This discovery could lead to new treatments for fungal infections by targeting the Sec2p gene.

Background

Aspergillus fumigatus is a filamentous fungus causing invasive aspergillosis in immunocompromised individuals. Regulating fungal growth is crucial for preventing disease development. The Sec2p gene encodes a guanine nucleotide exchange factor with unknown functions in A. fumigatus.

Objective

This study investigated the roles of the Sec2p gene in A. fumigatus growth, autophagy regulation, and pathogenicity. The researchers examined how Sec2p deletion affects fungal virulence, autophagy pathway function, and cell wall integrity responses.

Results

Deletion of Sec2p reduced colony growth by approximately 42% and increased autophagosome accumulation indicating inhibited autophagy. The ΔSec2p strain showed enhanced resistance to cell wall stressors and reduced virulence with 67% mouse survival compared to 22% for wild-type strains. Sec2p negatively regulated cell wall integrity pathway genes during stress and positively regulated autophagy pathways.

Conclusion

Sec2p positively regulates the autophagy pathway and negatively regulates the cell wall integrity pathway during stress, coordinating fungal growth and pathogenicity. Sec2p deletion reduced A. fumigatus virulence by disrupting autophagy-mediated nutrient homeostasis, suggesting it as a potential therapeutic target for treating fungal infections.
  • Published in:Journal of Fungi (Basel),
  • Study Type:Experimental Laboratory Study,
  • Source: PMID: 39852455
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