Competitiveness during Dual-Species Biofilm Formation of and and a Novel Treatment Strategy.

Annarita Falanga, Angela Maione, Alessandra La Pietra, Elisabetta de Alteriis, Stefania Vitale, Rosa Bellavita, Rosa Carotenuto, David Turrà, Stefania Galdiero, Emilia Galdiero, Marco Guida
Author Information
  1. Annarita Falanga: Department of Agricultural Science, University of Naples "Federico II", Via Università 100, 80055 Portici, Italy. ORCID
  2. Angela Maione: Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy. ORCID
  3. Alessandra La Pietra: Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy. ORCID
  4. Elisabetta de Alteriis: Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy. ORCID
  5. Stefania Vitale: Institute for Sustainable Plant Protection, National Research Council of Italy, 80055 Portici, Italy.
  6. Rosa Bellavita: Department of Pharmacy, School of Medicine, University of Naples "Federico II", Via Domenico Montesano 49, 80131 Naples, Italy. ORCID
  7. Rosa Carotenuto: Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy. ORCID
  8. David Turrà: Department of Agricultural Science, University of Naples "Federico II", Via Università 100, 80055 Portici, Italy. ORCID
  9. Stefania Galdiero: Department of Pharmacy, School of Medicine, University of Naples "Federico II", Via Domenico Montesano 49, 80131 Naples, Italy. ORCID
  10. Emilia Galdiero: Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy.
  11. Marco Guida: Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy. ORCID

Abstract

During an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as spp. and yeasts, such as spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species. is responsible for approximately 20% of human fusariosis, while is responsible for superficial mucosal and dermal infections and for disseminated bloodstream infections with a mortality rate above 40%. This study aims to investigate the interactions between and dual-species biofilm, considering variable formation conditions. Further, the ability of the WMR peptide, a modified version of myxinidin, to eradicate the mixed biofilm when used alone or in combination with fluconazole (FLC) was tested, and the efficacy of the combination of WMR and FLC at low doses was assessed, as well as its effect on the expression of some biofilm-related adhesin and hyphal regulatory genes. Finally, in order to confirm our findings in vivo and explore the synergistic effect of the two drugs, we utilized the infection model. We concluded that negatively affects growth in mixed biofilms. Combinatorial treatment by WMR and FLC significantly reduced the biomass and viability of both species in mature mixed biofilms, and these effects coincided with the reduced expression of biofilm-related genes in both fungi. Our results were confirmed in vivo since the synergistic antifungal activity of WMR and FLC increased the survival of infected larvae and reduced tissue invasion. These findings highlight the importance of drug combinations as an alternative treatment for and mixed biofilms.

Keywords

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