Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa

Detalhes bibliográficos
Autor(a) principal: Pimentel, Bruna Natália Alves da Silva [UNESP]
Data de Publicação: 2022
Outros Autores: Marin-Dett, Freddy Humberto [UNESP], Assis, Marcelo, Barbugli, Paula Aboud [UNESP], Longo, Elson, Vergani, Carlos Eduardo [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3389/fbioe.2022.826123
http://hdl.handle.net/11449/230465
Resumo: 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-AgVO3), silver tungstate (α-Ag2WO4), and silver molybdate (β-Ag2MoO4). 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-AgVO3, α-Ag2WO4, and β-Ag2MoO4. 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-AgVO3 (15.62 µg/ml) showed a decrease in cell viability. The antibiofilm activity of α-Ag2WO4 was similar to that of the standard drug (fluconazole). Although α-Ag2WO4 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-Ag2MoO4 inhibits the production of TNF-α in the infected model; however, it showed no antibiofilm activity. Based on the biocompatibility and antifungal findings, α-Ag2WO4 is a promising material for treating C. albicans infection.
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spelling Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa3D culturesCandida albicanscytokinesinfectionmicrocrystalssilverFungal 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-AgVO3), silver tungstate (α-Ag2WO4), and silver molybdate (β-Ag2MoO4). 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-AgVO3, α-Ag2WO4, and β-Ag2MoO4. 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-AgVO3 (15.62 µg/ml) showed a decrease in cell viability. The antibiofilm activity of α-Ag2WO4 was similar to that of the standard drug (fluconazole). Although α-Ag2WO4 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-Ag2MoO4 inhibits the production of TNF-α in the infected model; however, it showed no antibiofilm activity. Based on the biocompatibility and antifungal findings, α-Ag2WO4 is a promising material for treating C. albicans infection.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Estadual PaulistaLaboratory of Applied Microbiology Department of Dental Materials and Prosthodontics School of Dentistry São Paulo State University (UNESP)Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP)CDMF LIEC Chemistry Department Federal University of São Carlos (UFSCar)Laboratory of Applied Microbiology Department of Dental Materials and Prosthodontics School of Dentistry São Paulo State University (UNESP)Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP)FAPESP: 2013/07296-2 2018/01677-4CNPq: 431895/2016-3Universidade Estadual Paulista: 88887.335189/2019-00Universidade Estadual Paulista (UNESP)Universidade Federal de São Carlos (UFSCar)Pimentel, Bruna Natália Alves da Silva [UNESP]Marin-Dett, Freddy Humberto [UNESP]Assis, MarceloBarbugli, Paula Aboud [UNESP]Longo, ElsonVergani, Carlos Eduardo [UNESP]2022-04-29T08:40:06Z2022-04-29T08:40:06Z2022-02-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fbioe.2022.826123Frontiers in Bioengineering and Biotechnology, v. 10.2296-4185http://hdl.handle.net/11449/23046510.3389/fbioe.2022.8261232-s2.0-85125365595Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Bioengineering and Biotechnologyinfo:eu-repo/semantics/openAccess2024-06-21T15:18:45Zoai:repositorio.unesp.br:11449/230465Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T17:20:11.749181Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
title Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
spellingShingle Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
Pimentel, Bruna Natália Alves da Silva [UNESP]
3D cultures
Candida albicans
cytokines
infection
microcrystals
silver
title_short Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_full Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_fullStr Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_full_unstemmed Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
title_sort Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa
author Pimentel, Bruna Natália Alves da Silva [UNESP]
author_facet Pimentel, Bruna Natália Alves da Silva [UNESP]
Marin-Dett, Freddy Humberto [UNESP]
Assis, Marcelo
Barbugli, Paula Aboud [UNESP]
Longo, Elson
Vergani, Carlos Eduardo [UNESP]
author_role author
author2 Marin-Dett, Freddy Humberto [UNESP]
Assis, Marcelo
Barbugli, Paula Aboud [UNESP]
Longo, Elson
Vergani, Carlos Eduardo [UNESP]
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Universidade Federal de São Carlos (UFSCar)
dc.contributor.author.fl_str_mv Pimentel, Bruna Natália Alves da Silva [UNESP]
Marin-Dett, Freddy Humberto [UNESP]
Assis, Marcelo
Barbugli, Paula Aboud [UNESP]
Longo, Elson
Vergani, Carlos Eduardo [UNESP]
dc.subject.por.fl_str_mv 3D cultures
Candida albicans
cytokines
infection
microcrystals
silver
topic 3D cultures
Candida albicans
cytokines
infection
microcrystals
silver
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-AgVO3), silver tungstate (α-Ag2WO4), and silver molybdate (β-Ag2MoO4). 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-AgVO3, α-Ag2WO4, and β-Ag2MoO4. 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-AgVO3 (15.62 µg/ml) showed a decrease in cell viability. The antibiofilm activity of α-Ag2WO4 was similar to that of the standard drug (fluconazole). Although α-Ag2WO4 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-Ag2MoO4 inhibits the production of TNF-α in the infected model; however, it showed no antibiofilm activity. Based on the biocompatibility and antifungal findings, α-Ag2WO4 is a promising material for treating C. albicans infection.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-29T08:40:06Z
2022-04-29T08:40:06Z
2022-02-14
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fbioe.2022.826123
Frontiers in Bioengineering and Biotechnology, v. 10.
2296-4185
http://hdl.handle.net/11449/230465
10.3389/fbioe.2022.826123
2-s2.0-85125365595
url http://dx.doi.org/10.3389/fbioe.2022.826123
http://hdl.handle.net/11449/230465
identifier_str_mv Frontiers in Bioengineering and Biotechnology, v. 10.
2296-4185
10.3389/fbioe.2022.826123
2-s2.0-85125365595
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers in Bioengineering and Biotechnology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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