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Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa

Fungal infections have become a major concern in the medical community, especially those caused by Candida spp. Within this species, Candida albicans stands out for being an opportunistic commensal fungus that can cause superficial and invasive infections. Current antifungal therapy involves the loc...

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Autores principales: Pimentel, Bruna Natália Alves da Silva, Marin-Dett, Freddy Humberto, Assis, Marcelo, Barbugli, Paula Aboud, Longo, Elson, Vergani, Carlos Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883331/
https://www.ncbi.nlm.nih.gov/pubmed/35237581
http://dx.doi.org/10.3389/fbioe.2022.826123
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author Pimentel, Bruna Natália Alves da Silva
Marin-Dett, Freddy Humberto
Assis, Marcelo
Barbugli, Paula Aboud
Longo, Elson
Vergani, Carlos Eduardo
author_facet Pimentel, Bruna Natália Alves da Silva
Marin-Dett, Freddy Humberto
Assis, Marcelo
Barbugli, Paula Aboud
Longo, Elson
Vergani, Carlos Eduardo
author_sort Pimentel, Bruna Natália Alves da Silva
collection PubMed
description Fungal infections have become a major concern in the medical community, especially those caused by Candida spp. Within this species, Candida albicans stands out for being an opportunistic commensal fungus that can cause superficial and invasive infections. Current antifungal therapy involves the local and/or systemic use of drugs such as azoles, polyenes, and echinocandins. These antifungals are based on highly specific target sites, and the development of resistance may occur with changes in the enzymatic pathways that serve as the drug targets. Thus, the development of new antifungal drugs is highly recommended to prevent drug resistance. The present investigation evaluated the antifungal activity of silver-containing microcrystals such as silver vanadate (α-AgVO(3)), silver tungstate (α-Ag(2)WO(4)), and silver molybdate (β-Ag(2)MoO(4)). In addition to having antimicrobial activity, such compounds should not cause damage to underlying tissues. Thus, to better assess the biocompatibility of new compounds, a new three-dimensional (3D) coculture model involving three cell lines was developed. The validation of the model was based on fluorescent markers and confocal laser microscopy. The biocompatibility of silver-containing microcrystals was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 3D coculture was infected with C. albicans biofilm and challenged with α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4). The action of microcrystals on C. albicans biofilm was evaluated by colony-forming units (CFU/ml) and LIVE/DEAD staining. In addition, production of proinflammatory cytokines interleukin 6 (IL-6), IL-8, IL-1β, and tumor necrosis factor α (TNF-α) was measured by cytometric bead array kit using flow cytometry. The 3D coculture model described here proved to be adequate to assess both the biocompatibility of the new materials and the infectious processes. Regarding the biocompatibility of the microcrystals, only α-AgVO(3) (15.62 µg/ml) showed a decrease in cell viability. The antibiofilm activity of α-Ag(2)WO(4) was similar to that of the standard drug (fluconazole). Although α-Ag(2)WO(4) was able to induce the production of IL-6, IL-8, and IL-1β, no differences in cytokine production were observed between noninfected and infected models treated with this microcrystal. β-Ag(2)MoO(4) inhibits the production of TNF-α in the infected model; however, it showed no antibiofilm activity. Based on the biocompatibility and antifungal findings, α-Ag(2)WO(4) is a promising material for treating C. albicans infection.
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spelling pubmed-88833312022-03-01 Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa Pimentel, Bruna Natália Alves da Silva Marin-Dett, Freddy Humberto Assis, Marcelo Barbugli, Paula Aboud Longo, Elson Vergani, Carlos Eduardo Front Bioeng Biotechnol Bioengineering and Biotechnology Fungal infections have become a major concern in the medical community, especially those caused by Candida spp. Within this species, Candida albicans stands out for being an opportunistic commensal fungus that can cause superficial and invasive infections. Current antifungal therapy involves the local and/or systemic use of drugs such as azoles, polyenes, and echinocandins. These antifungals are based on highly specific target sites, and the development of resistance may occur with changes in the enzymatic pathways that serve as the drug targets. Thus, the development of new antifungal drugs is highly recommended to prevent drug resistance. The present investigation evaluated the antifungal activity of silver-containing microcrystals such as silver vanadate (α-AgVO(3)), silver tungstate (α-Ag(2)WO(4)), and silver molybdate (β-Ag(2)MoO(4)). In addition to having antimicrobial activity, such compounds should not cause damage to underlying tissues. Thus, to better assess the biocompatibility of new compounds, a new three-dimensional (3D) coculture model involving three cell lines was developed. The validation of the model was based on fluorescent markers and confocal laser microscopy. The biocompatibility of silver-containing microcrystals was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 3D coculture was infected with C. albicans biofilm and challenged with α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4). The action of microcrystals on C. albicans biofilm was evaluated by colony-forming units (CFU/ml) and LIVE/DEAD staining. In addition, production of proinflammatory cytokines interleukin 6 (IL-6), IL-8, IL-1β, and tumor necrosis factor α (TNF-α) was measured by cytometric bead array kit using flow cytometry. The 3D coculture model described here proved to be adequate to assess both the biocompatibility of the new materials and the infectious processes. Regarding the biocompatibility of the microcrystals, only α-AgVO(3) (15.62 µg/ml) showed a decrease in cell viability. The antibiofilm activity of α-Ag(2)WO(4) was similar to that of the standard drug (fluconazole). Although α-Ag(2)WO(4) was able to induce the production of IL-6, IL-8, and IL-1β, no differences in cytokine production were observed between noninfected and infected models treated with this microcrystal. β-Ag(2)MoO(4) inhibits the production of TNF-α in the infected model; however, it showed no antibiofilm activity. Based on the biocompatibility and antifungal findings, α-Ag(2)WO(4) is a promising material for treating C. albicans infection. Frontiers Media S.A. 2022-02-14 /pmc/articles/PMC8883331/ /pubmed/35237581 http://dx.doi.org/10.3389/fbioe.2022.826123 Text en Copyright © 2022 Pimentel, Marin-Dett, Assis, Barbugli, Longo and Vergani. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Pimentel, Bruna Natália Alves da Silva
Marin-Dett, Freddy Humberto
Assis, Marcelo
Barbugli, Paula Aboud
Longo, Elson
Vergani, Carlos Eduardo
Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa
title Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_full Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_fullStr Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_full_unstemmed Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_short Antifungal Activity and Biocompatibility of α-AgVO(3), α-Ag(2)WO(4), and β-Ag(2)MoO(4) Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_sort antifungal activity and biocompatibility of α-agvo(3), α-ag(2)wo(4), and β-ag(2)moo(4) using a three-dimensional coculture model of the oral mucosa
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883331/
https://www.ncbi.nlm.nih.gov/pubmed/35237581
http://dx.doi.org/10.3389/fbioe.2022.826123
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