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HIV protease inhibitors restore amphotericin B activity against Candida

Summary

Researchers discovered that HIV protease inhibitors, medications commonly used to treat HIV, can significantly enhance the effectiveness of amphotericin B, a powerful antifungal drug. When combined, these medications work synergistically to kill the dangerous fungus Candida auris, reduce its ability to form protective biofilms, and lower infection levels. This finding suggests a promising new treatment strategy for multidrug-resistant fungal infections that currently pose a serious global health threat.

Background

Candida auris is a multidrug-resistant fungal pathogen causing severe systemic infections with high mortality rates. Approximately 30% of C. auris isolates demonstrate resistance to amphotericin B, one of the most powerful antifungal agents. Novel antifungal therapies are urgently needed to combat this emerging pathogen.

Objective

To identify compounds that potentiate amphotericin B activity against C. auris and evaluate their efficacy against biofilm formation, hyphal growth, and fungal burden in vivo. The study aimed to determine if HIV protease inhibitors could restore antifungal activity and reduce toxicity when combined with amphotericin B.

Results

Four HIV protease inhibitors (atazanavir, saquinavir, lopinavir, and ritonavir) demonstrated synergistic interactions with amphotericin B against all 15 C. auris isolates tested (FICI 0.09-0.50). Combinations showed fungicidal effects within 6 hours, inhibited biofilm formation by 60-75%, suppressed C. albicans hyphae, and reduced C. auris burden by 1.7-2.6 Log10 in the C. elegans model.

Conclusion

HIV protease inhibitors in combination with amphotericin B represent promising candidates for developing novel antifungal therapies against multidrug-resistant Candida infections. The combinations effectively restore amphotericin B activity, target virulence factors, and demonstrate significant in vivo efficacy warranting further clinical investigation.
  • Published in:PLoS One,
  • Study Type:In vitro and In vivo Experimental Study,
  • Source: PMID: 40440253, DOI: 10.1371/journal.pone.0324080
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