Products Cited in Publications Worldwide HIV protease inhibitors restore amphotericin B activity against Candida

HIV protease inhibitors restore amphotericin B activity against Candida

Elgammal, Yehia; Salama, Ehab A; Seleem, Mohamed N

DOI: PMID:

Abstract

Candida auris is an invasive fungal pathogen, representing a global public health threat. It is characterized by high mortality rates among infected individuals, significant resistance, and a remarkable ability to persist in healthcare environments. While is one of the most powerful agents for treating Candida infections, approximately 30% of C. auris isolates demonstrate resistance to it. Thus, the development of novel therapies is vital for tackling its life-threatening infections. In this study, we identified four HIV protease inhibitors (, , and ) as strong potentiators of against C. auris. A synergistic effect between HIV protease inhibitors and was observed against 15 C. auris isolates with fractional inhibitory concentration index (FICI) ranging from 0.09 to 0.50. Additionally, the combinations between HIV protease inhibitors and showed fungicidal effect, significantly reducing the viable cell count in the time-kill assay within 6 hours. Furthermore, the combinations inhibited biofilm formation of C. auris by 60–75% and exhibited a remarkable suppression of C. albicans hyphae. The in vivo treatment with HIV protease inhibitors combined with resulted in a significant reduction of C. auris colony-forming units (CFU) by 1.7–2.6 Log10 in the C. elegans model. These findings suggest that HIV protease inhibitors, in combination with , are promising candidates for the development of novel drugs to treat Candida infections.

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