Nanoemulsion Increases the Antifungal Activity of Amphotericin B against Four Candida auris Clades: In Vitro and In Vivo Assays

Author:

Marena Gabriel Davi123ORCID,Ruiz-Gaitán Alba14ORCID,Garcia-Bustos Victor15,Tormo-Mas María Ángeles1ORCID,Pérez-Royo Jose Manuel1ORCID,López Alejandro1,Bernarbe Patricia1,Pérez Ruiz María Dolores6,Zaragoza Macian Lara6,Vicente Saez Carmen6,Avalos Mansilla Antonia6,Gómez Eulogio Valentín17ORCID,Carvalho Gabriela Corrêa23ORCID,Bauab Tais Maria3,Chorilli Marlus2ORCID,Pemán Javier14ORCID

Affiliation:

1. Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain

2. Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil

3. Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil

4. Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain

5. Department of Pathology, Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain

6. Department of Pathological Anatomy, La Fe Hospital, 46026 Valencia, Spain

7. Department of Microbiology and Ecology, University of Valencia, 46010 Valencia, Spain

Abstract

Candida auris is an emerging yeast of worldwide interest due to its antifungal resistance and mortality rates. The aim of this study was to analyse the in vitro and in vivo antifungal activity of a nanoemulsion loaded with amphotericin B (NEA) against planktonic cells and biofilm of C. auris clinical isolates belonging to four different clades. In vivo assays were performed using the Galleria mellonella model to analyse antifungal activity and histopathological changes. The in vitro results showed that NEA exhibited better antifungal activity than free amphotericin B (AmB) in both planktonic and sessile cells, with >31% inhibition of mature biofilm. In the in vivo assays, NEA demonstrated superior antifungal activity in both haemolymph and tissue. NEA reduced the fungal load in the haemolymph more rapidly and with more activity in the first 24 h after infection. The histological analysis of infected larvae revealed clusters of yeast, immune cells, melanisation, and granulomas. In conclusion, NEA significantly improved the in vitro and in vivo antifungal activity of AmB and could be considered a promising therapy for C. auris infections.

Funder

São Paulo Research Foundation—FAPESP

Publisher

MDPI AG

Subject

Virology,Microbiology (medical),Microbiology

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