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. 2025 Apr;13(4):e0178624.
doi: 10.1128/spectrum.01786-24. Epub 2025 Feb 27.

In vitro activities of lipopeptides against fluconazole-resistant Candida auris

Simona Fioriti  1 , Francesco Pallotta  1 , Gloria D'Achille  1 , Oscar Cirioni  1   2 , Oriana Simonetti  3 , Damian Neubauer  4 , Elzbieta Kamysz  5 , Wojciech Kamysz  4 , Lucia Brescini  1   2 , Sara Caucci  1 , Giuseppina Caggiano  6 , Andrea Giacometti  1   2 , Gianluca Morroni  1 , Francesco Barchiesi  1   7
Affiliations

In vitro activities of lipopeptides against fluconazole-resistant Candida auris

Simona Fioriti et al. Microbiol Spectr. 2025 Apr.

Abstract

Candida auris has increasingly become a global threat due to its wide range of antifungal resistances as well as its ability to sustain outbreaks in clinical settings. Two lipopeptides, C14-NleRR-NH2 (Nel) and C14-WRR-NH2 (WR), were evaluated against six fluconazole-resistant C. auris isolates. Both molecules showed good antimicrobial activity as demonstrated by MIC determination, time-kill, and microscopy experiments. The peptides were able to inhibit fungal growth, while sub-MIC concentrations of the molecules delayed the growth. Moreover, the combinations of the two peptides with fluconazole demonstrated a reciprocal potentiation by checkerboard and time-kill experiments. Our results showed that antimicrobial peptides could be a promising option for the treatment of antifungal-resistant C. auris.IMPORTANCEAs well as antibiotics, also in fungal infections, antimicrobial resistance increased over the years. Moreover, in the last years, a new species emerged, Candida auris, as a nosocomial pathogen. C. auris possesses intrinsic resistance to common antifungals, such as azoles, that complicate therapeutic options. The combination of these two elements poses a risk for the treatment of fungal infections in the next years. The search for novel compounds with antimicrobial properties is crucial for the treatment of infections to overcome the increasing resistance of these etiological agents.

Keywords: Candida auris; fluconazole; in vitro activity; peptides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Growth curves and microscopy. (A) C. auris 728157 treated with NeI (P <0.05 after 8 hours of treatment for all the concentrations compared to control); (B) C. auris 728157 treated with WR (P <0.05 after 9 hours of treatment for all the concentrations compared to control); (C) C. auris CAB-1 treated with NeI (P <0.05 after 8 hours of treatment for 1X and 2X MIC concentrations compared to control); (D) C. auris CAB-1 treated with WR (P <0.05 after 9 hours of treatment for all the concentrations compared to control); (E) C. auris CAB-2 treated with NeI (P <0.05 after 7 hours of treatment for 1X and 2X MIC concentrations compared to control); (F) C. auris CAB-2 treated with WR (P <0.05 after 8 hours of treatment for all the concentrations compared to control). CRT, control. Microscopy images with 60× magnification of isolate 728157 after 24 hours of incubation at 37°C: (G) untreated; (H) fluconazole 128 µg/mL; (I) NeI 0.5X MIC; (L) WR 0.5X MIC.
Fig 2
Fig 2
Checkerboard heatmap. (A) C. auris 728157 fluconazole and Nel combination; (B) C. auris 728157 fluconazole and WR combination; (C) C. auris CAB-1 fluconazole and Nel combination; (D) C. auris CAB-1 fluconazole and WR combination; (E) C. auris CAB-2 fluconazole and Nel combination; (F) C. auris CAB-2 fluconazole and WR combination.
See this image and copyright information in PMC

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