Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment Strategy
During an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as <i>Fusarium</i> spp. and yeasts, such as <i>Candida</i> spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/6/1167 |
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| author | 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_facet | 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_sort | Annarita Falanga |
| collection | DOAJ |
| description | During an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as <i>Fusarium</i> spp. and yeasts, such as <i>Candida</i> spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species. <i>Fusarium oxysporum</i> is responsible for approximately 20% of human fusariosis, while <i>Candida albicans</i> 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 <i>C. albicans</i> and <i>F. oxysporum</i> 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 <i>Galleria mellonella</i> infection model. We concluded that <i>C. albicans</i> negatively affects <i>F. oxysporum</i> 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 <i>C. albicans</i> and <i>F. oxysporum</i> mixed biofilms. |
| first_indexed | 2024-03-09T22:45:29Z |
| format | Article |
| id | doaj.art-6bebab54560246d39d6f2cec65e0b8e3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:45:29Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6bebab54560246d39d6f2cec65e0b8e32023-11-23T18:29:20ZengMDPI AGPharmaceutics1999-49232022-05-01146116710.3390/pharmaceutics14061167Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment StrategyAnnarita Falanga0Angela Maione1Alessandra La Pietra2Elisabetta de Alteriis3Stefania Vitale4Rosa Bellavita5Rosa Carotenuto6David Turrà7Stefania Galdiero8Emilia Galdiero9Marco Guida10Department of Agricultural Science, University of Naples “Federico II”, Via Università 100, 80055 Portici, ItalyDepartment of Biology, University of Naples ‘Federico II’, Via Cinthia, 80126 Naples, ItalyDepartment of Biology, University of Naples ‘Federico II’, Via Cinthia, 80126 Naples, ItalyDepartment of Biology, University of Naples ‘Federico II’, Via Cinthia, 80126 Naples, ItalyInstitute for Sustainable Plant Protection, National Research Council of Italy, 80055 Portici, ItalyDepartment of Pharmacy, School of Medicine, University of Naples “Federico II”, Via Domenico Montesano 49, 80131 Naples, ItalyDepartment of Biology, University of Naples ‘Federico II’, Via Cinthia, 80126 Naples, ItalyDepartment of Agricultural Science, University of Naples “Federico II”, Via Università 100, 80055 Portici, ItalyDepartment of Pharmacy, School of Medicine, University of Naples “Federico II”, Via Domenico Montesano 49, 80131 Naples, ItalyDepartment of Biology, University of Naples ‘Federico II’, Via Cinthia, 80126 Naples, ItalyDepartment of Biology, University of Naples ‘Federico II’, Via Cinthia, 80126 Naples, ItalyDuring an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as <i>Fusarium</i> spp. and yeasts, such as <i>Candida</i> spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species. <i>Fusarium oxysporum</i> is responsible for approximately 20% of human fusariosis, while <i>Candida albicans</i> 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 <i>C. albicans</i> and <i>F. oxysporum</i> 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 <i>Galleria mellonella</i> infection model. We concluded that <i>C. albicans</i> negatively affects <i>F. oxysporum</i> 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 <i>C. albicans</i> and <i>F. oxysporum</i> mixed biofilms.https://www.mdpi.com/1999-4923/14/6/1167<i>Fusarium oxysporum</i><i>Candida albicans</i>polymicrobial biofilmWMR<i>Galleria mellonella</i> |
| spellingShingle | Annarita Falanga Angela Maione Alessandra La Pietra Elisabetta de Alteriis Stefania Vitale Rosa Bellavita Rosa Carotenuto David Turrà Stefania Galdiero Emilia Galdiero Marco Guida Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment Strategy Pharmaceutics <i>Fusarium oxysporum</i> <i>Candida albicans</i> polymicrobial biofilm WMR <i>Galleria mellonella</i> |
| title | Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment Strategy |
| title_full | Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment Strategy |
| title_fullStr | Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment Strategy |
| title_full_unstemmed | Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment Strategy |
| title_short | Competitiveness during Dual-Species Biofilm Formation of <i>Fusarium oxysporum</i> and <i>Candida albicans</i> and a Novel Treatment Strategy |
| title_sort | competitiveness during dual species biofilm formation of i fusarium oxysporum i and i candida albicans i and a novel treatment strategy |
| topic | <i>Fusarium oxysporum</i> <i>Candida albicans</i> polymicrobial biofilm WMR <i>Galleria mellonella</i> |
| url | https://www.mdpi.com/1999-4923/14/6/1167 |
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