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The cyclase-associated protein contributes to antifungal susceptibility and virulence in Aspergillus fumigatus

Summary

Researchers found that removing a specific protein called CAP from a dangerous mold called Aspergillus fumigatus makes it much weaker and easier to kill with antifungal drugs. This mold normally causes serious lung infections in people with weak immune systems. The study showed that CAP helps the mold grow and resist medicines, and blocking it could be a new way to treat these dangerous infections.

Background

Aspergillus fumigatus is the most prevalent pathogenic mould causing invasive aspergillosis with high morbidity and mortality in immunocompromised patients. The cyclase-associated protein (CAP) has been shown to regulate growth and virulence in other fungal species but its role in A. fumigatus antifungal susceptibility remains unclear.

Objective

To characterize the functions of cyclase-associated protein (CAP) in A. fumigatus virulence and antifungal susceptibility. This study aimed to determine how CAP gene knockout affects fungal growth, cell wall integrity, stress responses, and response to antifungal agents.

Results

ΔCAP showed reduced growth rates, abnormal hyphal development, and increased susceptibility to cell wall-perturbing agents, oxidative stress-inducing agents, calcineurin inhibitors, and triazoles. CAP interacts with actin and adenylate cyclase, and ΔCAP exhibited downregulated actin expression, impaired AC-cAMP-PKA pathway activity, and decreased efflux pump gene expression. In vivo studies demonstrated attenuated virulence and enhanced voriconazole efficacy in ΔCAP-infected mice.

Conclusion

CAP plays essential roles in regulating antifungal susceptibility and virulence in A. fumigatus through interactions with actin and the AC-cAMP-PKA signaling pathway. CAP may serve as a potential novel therapeutic target for improving treatment efficacy in invasive aspergillosis.
  • Published in:Emerging Microbes & Infections,
  • Study Type:Experimental Study,
  • Source: PMID: 40396792, DOI: 10.1080/22221751.2025.2506795
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