Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/cimb44110364 http://hdl.handle.net/11449/249358 |
Resumo: | Candida albicans is the chief etiological agent of candidiasis, a mycosis prevalent in individuals with acquired immunodeficiency syndrome (AIDS). In recent years, the introduction of human immunodeficiency virus (HIV) protease inhibitors (HIV-PI) has reduced the prevalence of candidiasis in these patients. Seeking new therapeutic strategies based on the perspective of drug repositioning, we evaluated the effects of two second-generation HIV-PIs, atazanavir (ATV) and darunavir (DRV), on virulence factors of C. albicans and experimental candidiasis. For this, clinical strains of C. albicans were subjected to in vitro and in vivo treatments with ATV or DRV. As a result, ATV and DRV exhibited antifungal activity against fungal cells at 512 μg/mL, reduced the viability and biomass of biofilms, and inhibited filamentation of C. albicans. In addition, these HIV-PIs downregulated the expression of SAP2 and BRC1 genes of C. albicans. In an in vivo study, prophylactic use of ATV and DRV prolonged the survival rate of Galleria mellonella larvae infected with C. albicans. Therefore, ATV and DRV showed activity against C. albicans by reducing cell growth, biofilm formation, filamentation, and expression of virulence genes. Furthermore, ATV and DRV decreased experimental candidiasis, suggesting the repurposing of HIV-PIs as antifungal treatments for C. albicans infections. |
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Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Studyatazanavir sulfateCandida albicansdarunavirHIVprotease inhibitorsvirulence factorsCandida albicans is the chief etiological agent of candidiasis, a mycosis prevalent in individuals with acquired immunodeficiency syndrome (AIDS). In recent years, the introduction of human immunodeficiency virus (HIV) protease inhibitors (HIV-PI) has reduced the prevalence of candidiasis in these patients. Seeking new therapeutic strategies based on the perspective of drug repositioning, we evaluated the effects of two second-generation HIV-PIs, atazanavir (ATV) and darunavir (DRV), on virulence factors of C. albicans and experimental candidiasis. For this, clinical strains of C. albicans were subjected to in vitro and in vivo treatments with ATV or DRV. As a result, ATV and DRV exhibited antifungal activity against fungal cells at 512 μg/mL, reduced the viability and biomass of biofilms, and inhibited filamentation of C. albicans. In addition, these HIV-PIs downregulated the expression of SAP2 and BRC1 genes of C. albicans. In an in vivo study, prophylactic use of ATV and DRV prolonged the survival rate of Galleria mellonella larvae infected with C. albicans. Therefore, ATV and DRV showed activity against C. albicans by reducing cell growth, biofilm formation, filamentation, and expression of virulence genes. Furthermore, ATV and DRV decreased experimental candidiasis, suggesting the repurposing of HIV-PIs as antifungal treatments for C. albicans infections.Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (Unesp), São PauloMulticampi School of Medical Sciences Federal University of Rio Grande do Norte (UFRN), Rio Grande do NorteDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (Unesp), São PauloUniversidade Estadual Paulista (UNESP)Federal University of Rio Grande do Norte (UFRN)Fenley, Juliana de C. [UNESP]de Barros, Patrícia P. [UNESP]Carmo, Paulo H. F. do [UNESP]Garcia, Maíra T. [UNESP]Rossoni, Rodnei D. [UNESP]Junqueira, Juliana C. [UNESP]2023-07-29T15:13:51Z2023-07-29T15:13:51Z2022-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5379-5389http://dx.doi.org/10.3390/cimb44110364Current Issues in Molecular Biology, v. 44, n. 11, p. 5379-5389, 2022.1467-30451467-3037http://hdl.handle.net/11449/24935810.3390/cimb441103642-s2.0-85141619011Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCurrent Issues in Molecular Biologyinfo:eu-repo/semantics/openAccess2023-07-29T15:13:51Zoai:repositorio.unesp.br:11449/249358Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:39:34.600034Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study |
title |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study |
spellingShingle |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study Fenley, Juliana de C. [UNESP] atazanavir sulfate Candida albicans darunavir HIV protease inhibitors virulence factors |
title_short |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study |
title_full |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study |
title_fullStr |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study |
title_full_unstemmed |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study |
title_sort |
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study |
author |
Fenley, Juliana de C. [UNESP] |
author_facet |
Fenley, Juliana de C. [UNESP] de Barros, Patrícia P. [UNESP] Carmo, Paulo H. F. do [UNESP] Garcia, Maíra T. [UNESP] Rossoni, Rodnei D. [UNESP] Junqueira, Juliana C. [UNESP] |
author_role |
author |
author2 |
de Barros, Patrícia P. [UNESP] Carmo, Paulo H. F. do [UNESP] Garcia, Maíra T. [UNESP] Rossoni, Rodnei D. [UNESP] Junqueira, Juliana C. [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Federal University of Rio Grande do Norte (UFRN) |
dc.contributor.author.fl_str_mv |
Fenley, Juliana de C. [UNESP] de Barros, Patrícia P. [UNESP] Carmo, Paulo H. F. do [UNESP] Garcia, Maíra T. [UNESP] Rossoni, Rodnei D. [UNESP] Junqueira, Juliana C. [UNESP] |
dc.subject.por.fl_str_mv |
atazanavir sulfate Candida albicans darunavir HIV protease inhibitors virulence factors |
topic |
atazanavir sulfate Candida albicans darunavir HIV protease inhibitors virulence factors |
description |
Candida albicans is the chief etiological agent of candidiasis, a mycosis prevalent in individuals with acquired immunodeficiency syndrome (AIDS). In recent years, the introduction of human immunodeficiency virus (HIV) protease inhibitors (HIV-PI) has reduced the prevalence of candidiasis in these patients. Seeking new therapeutic strategies based on the perspective of drug repositioning, we evaluated the effects of two second-generation HIV-PIs, atazanavir (ATV) and darunavir (DRV), on virulence factors of C. albicans and experimental candidiasis. For this, clinical strains of C. albicans were subjected to in vitro and in vivo treatments with ATV or DRV. As a result, ATV and DRV exhibited antifungal activity against fungal cells at 512 μg/mL, reduced the viability and biomass of biofilms, and inhibited filamentation of C. albicans. In addition, these HIV-PIs downregulated the expression of SAP2 and BRC1 genes of C. albicans. In an in vivo study, prophylactic use of ATV and DRV prolonged the survival rate of Galleria mellonella larvae infected with C. albicans. Therefore, ATV and DRV showed activity against C. albicans by reducing cell growth, biofilm formation, filamentation, and expression of virulence genes. Furthermore, ATV and DRV decreased experimental candidiasis, suggesting the repurposing of HIV-PIs as antifungal treatments for C. albicans infections. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11-01 2023-07-29T15:13:51Z 2023-07-29T15:13:51Z |
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/10.3390/cimb44110364 Current Issues in Molecular Biology, v. 44, n. 11, p. 5379-5389, 2022. 1467-3045 1467-3037 http://hdl.handle.net/11449/249358 10.3390/cimb44110364 2-s2.0-85141619011 |
url |
http://dx.doi.org/10.3390/cimb44110364 http://hdl.handle.net/11449/249358 |
identifier_str_mv |
Current Issues in Molecular Biology, v. 44, n. 11, p. 5379-5389, 2022. 1467-3045 1467-3037 10.3390/cimb44110364 2-s2.0-85141619011 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Current Issues in Molecular Biology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
5379-5389 |
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) |
repository.mail.fl_str_mv |
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1808129345263239168 |