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Therapeutic Use of the Antimicrobial Peptide PNR20 to Resolve Disseminated Candidiasis in a Murine Model
Jeisson Micelly-Moreno1,2, Adriana Barreto-Santamaría3, Gabriela Arévalo-Pinzón4
1Faculty of Health Sciences, Universidad Colegio Mayor de Cundinamarca, Bogota 110311, Colombia.
Abstract:
Invasive fungal infections (IFIs) caused by Candida species are an emerging threat globally, given that patients at-risk and antifungal resistance are increasing. Antimicrobial peptides (AMPs) have shown good therapeutic capacity against different multidrug-resistant (MDR) microorganisms. This study evaluated the activity of the synthetic peptide, PNR20, against Candida albicans ATCC 10231 and a MDR Colombian clinical isolate of Candida auris. Perturbation of yeast cell surface was evaluated using scanning electron microscopy. Cell viability of Vero cells was determined to assess peptide toxicity. Additionally, survival, fungal burden, and histopathology of BALB/c mice infected intravenously with each Candida species and treated with PNR20 were analyzed. Morphological alterations were identified in both species, demonstrating the antifungal effect of PNR20. In vitro, Vero cells' viability was not affected by PNR20. All mice infected with either C. albicans or C. auris and treated with PNR20 survived and had a significant reduction in the fungal burden in the kidney compared to the control group. The histopathological analysis in mice infected and treated with PNR20 showed more preserved tissues, without the presence of yeast, compared to the control groups. This work shows that the utilization of PNR20 is a promising therapeutic alternative against disseminated candidiasis.
Insights
The synthetic peptide PNR20 effectively combats invasive fungal infections caused by Candida species, including drug-resistant Candida auris. PNR20 demonstrated significant antifungal activity and improved survival rates in infected mice.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive fungal infections (IFIs) caused by Candida species pose a growing global health threat due to increasing at-risk populations and antifungal resistance.
- Antimicrobial peptides (AMPs) are emerging as a promising therapeutic strategy against multidrug-resistant (MDR) microorganisms.
Purpose of the Study:
- To evaluate the efficacy of the synthetic peptide PNR20 against Candida albicans and a multidrug-resistant Candida auris clinical isolate.
- To assess the in vivo therapeutic potential of PNR20 in a murine model of disseminated candidiasis.
Main Methods:
- In vitro antifungal activity was assessed against Candida albicans and Candida auris.
- Scanning electron microscopy was used to evaluate yeast cell surface perturbation.
- In vivo studies involved assessing survival, fungal burden, and histopathology in PNR20-treated infected mice.
Main Results:
- PNR20 induced morphological alterations in both Candida species, indicating antifungal effects.
- In vitro, PNR20 showed no toxicity to Vero cells.
- All PNR20-treated mice survived, exhibiting reduced kidney fungal burden and preserved tissue histology compared to controls.
Conclusions:
- The synthetic peptide PNR20 exhibits potent antifungal activity against Candida species, including MDR Candida auris.
- PNR20 demonstrates a favorable safety profile and therapeutic efficacy in a murine model of disseminated candidiasis.
- PNR20 represents a promising alternative therapeutic agent for treating invasive fungal infections.
