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Published on: February 14, 2018
In vitro activities of lipopeptides against fluconazole-resistant Candida auris
Simona Fioriti1, Francesco Pallotta1, Gloria D'Achille1
1Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona, Italy.
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.
Insights
Novel antimicrobial peptides show promise against drug-resistant Candida auris infections. These lipopeptides, Nel and WR, effectively inhibited fungal growth and potentiated fluconazole, offering a potential new strategy for treating resistant fungal infections.
Area of Science:
- Mycology
- Infectious Diseases
- Drug Discovery
Background:
- Candida auris is a growing global health concern due to widespread antifungal resistance and its propensity for clinical outbreaks.
- This multidrug-resistant yeast poses significant therapeutic challenges, particularly its intrinsic resistance to azole antifungals like fluconazole.
- The emergence of Candida auris necessitates the development of novel treatment strategies to combat resistant fungal infections.
Purpose of the Study:
- To evaluate the efficacy of two novel lipopeptides, C14-NleRR-NH2 (Nel) and C14-WRR-NH2 (WR), against fluconazole-resistant Candida auris isolates.
- To assess the antimicrobial activity of these peptides individually and in combination with fluconazole.
- To explore the potential of antimicrobial peptides as a therapeutic option for Candida auris infections.
Main Methods:
- Minimum Inhibitory Concentration (MIC) determination.
- Time-kill assays and microscopy experiments to assess fungal growth inhibition.
- Checkerboard assays to evaluate synergistic effects in peptide-fluconazole combinations.
Main Results:
- Both lipopeptides, Nel and WR, demonstrated significant antimicrobial activity against six fluconazole-resistant Candida auris isolates.
- Peptides inhibited fungal growth, with sub-inhibitory concentrations delaying growth.
- Combinations of Nel and WR with fluconazole showed synergistic potentiation, enhancing antifungal efficacy.
Conclusions:
- Antimicrobial peptides Nel and WR are effective against drug-resistant Candida auris.
- The synergistic effect observed with fluconazole suggests a promising combination therapy approach.
- These findings highlight antimicrobial peptides as a potential therapeutic avenue for treating challenging Candida auris infections.
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