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A human-relevant alternative infection model for mucormycosis using the silkworm Bombyx mori

Summary

Scientists developed a new way to test antifungal drugs using silkworms instead of expensive and ethically problematic mammal studies. They infected silkworms with mucormycosis-causing fungi and found that the infections behaved similarly to human cases, especially when they simulated human risk factors like steroid use and iron overload. The silkworm model successfully demonstrated that existing antifungal drugs work, while also revealing differences in fungal virulence that were linked to specific surface proteins.

Background

Mucormycosis is a life-threatening opportunistic infection caused by Mucorales fungi with high mortality rates and limited antifungal therapies. These fungi naturally resist existing antifungal agents and traditional mammalian models are expensive and raise ethical concerns, limiting large-scale studies.

Objective

To establish a silkworm (Bombyx mori) infection model to investigate Mucorales pathogenicity and evaluate its relevance to human infection, including assessment of clinical risk factors and antifungal drug efficacy.

Results

Multiple Mucorales species induced fatal infections in silkworms with strain-dependent LD50 values showing up to 54-fold differences. Clinical risk factors significantly reduced LD50, and isavuconazonium prolonged survival in infected silkworms. High-molecular weight (50-100 kDa) cell surface proteins were associated with increased pathogenicity.

Conclusion

The silkworm model is a viable, human-relevant alternative for investigating Mucorales infections and screening antimycotic drugs, with potential for large-scale studies and elucidation of host-pathogen molecular mechanisms.
  • Published in:PLoS One,
  • Study Type:Experimental Animal Model Study,
  • Source: PMID: 40997068, DOI: 10.1371/journal.pone.0333476
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