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

Summary

Researchers developed a silkworm-based model to study mucormycosis, a deadly fungal infection. The model reproduces the same disease patterns and risk factors seen in humans, including effects of steroids and iron levels. Importantly, it successfully predicted how well antifungal drugs work against the infection, offering a faster and more ethical alternative to mammal testing for developing new treatments.

Background

Mucormycosis is a life-threatening opportunistic infection caused by Mucorales fungi with high mortality rates of 44-54%. Traditional mammalian infection models are expensive and raise ethical concerns, limiting their use for large-scale studies. Alternative infection models are needed for antifungal drug screening and investigation of pathogenic mechanisms.

Objective

To establish a silkworm (Bombyx mori) infection model for investigating Mucorales pathogenicity and evaluating its relevance to human infection. The study aimed to assess whether this model can be used for antifungal screening and to explore molecular mechanisms of pathogenicity.

Results

All three Mucorales species induced fatal infections in silkworms with hyphal invasion patterns resembling human mucormycosis. Steroid use and iron overload significantly reduced LD50 values. Isavuconazonium treatment prolonged survival of infected silkworms. Up to 100-fold differences in pathogenicity among R. arrhizus strains correlated with high-molecular weight (50-100 kDa) cell surface proteins.

Conclusion

The silkworm model is viable and human-relevant for investigating Mucorales infections, demonstrating similar pathogenic mechanisms and risk factors to human disease. This model shows potential for large-scale antimucormycosis drug screening and elucidating host-pathogen molecular interactions.
  • Published in:PLoS One,
  • Study Type:Experimental infection model study,
  • Source: 10.1371/journal.pone.0333476; PMID: 40997068
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