Therapeutic Use of the Antimicrobial Peptide PNR20 to Resolve Disseminated Candidiasis in a Murine Model

Author:

Micelly-Moreno Jeisson12ORCID,Barreto-Santamaría Adriana3ORCID,Arévalo-Pinzón Gabriela4ORCID,Firacative Carolina2ORCID,Gómez Beatriz L.2ORCID,Escandón Patricia5ORCID,Patarroyo Manuel A.67ORCID,Muñoz Julián E.28ORCID

Affiliation:

1. Faculty of Health Sciences, Universidad Colegio Mayor de Cundinamarca, Bogota 110311, Colombia

2. Studies in Translational Microbiology and Emerging Diseases (MICROS) Research Group, School of Medicine and Health Sciences, Universidad de Rosario, Bogota 111221, Colombia

3. Receptor-Ligand Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogota 111321, Colombia

4. Microbiology Department, Faculty of Sciences, Pontificia Universidad Javeriana, Carrera 7 #40–62, Bogota 110231, Colombia

5. Microbiology Group, Instituto Nacional de Salud, Bogota 111321, Colombia

6. Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogota 111321, Colombia

7. Microbiology Department, Faculty of Medicine, Universidad Nacional de Colombia, Bogota 111321, Colombia

8. Public Health Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Bogota 111221, 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.

Funder

Colombia’s Ministry of Science, Technology, and Innovation

School of Medicine and Health Sciences (ABN122), Universidad del Rosario, Bogotá D.C., Colombia

Publisher

MDPI AG

Subject

Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)

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