Are the Statins promising antifungal agents against invasive candidiasis?
The medical importance of intra-abdominal candidiasis (IAC) contrasts with the limited number of pharmacological treatment options available and the increasing rate of resistance to antifungal drugs. Thus, the repositioning of compounds in clinical use can contribute to the broadening of treatment p...
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Format: | Article |
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Elsevier
2019-03-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332218346602 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
William Gustavo Lima Lídia Anita Alves-Nascimento Jéssica Tauany Andrade Letícia Vieira Rosy Iara Maciel de Azambuja Ribeiro Ralph Gruppi Thomé Hélio Batista dos Santos Jaqueline Maria Siqueira Ferreira Adriana Cristina Soares |
spellingShingle |
William Gustavo Lima Lídia Anita Alves-Nascimento Jéssica Tauany Andrade Letícia Vieira Rosy Iara Maciel de Azambuja Ribeiro Ralph Gruppi Thomé Hélio Batista dos Santos Jaqueline Maria Siqueira Ferreira Adriana Cristina Soares Are the Statins promising antifungal agents against invasive candidiasis? Biomedicine & Pharmacotherapy Candida albicans Biofilm Yeast-to-hyphal transition Synergism Fluvastatin Intra-abdominal candidiasis |
author_facet |
William Gustavo Lima Lídia Anita Alves-Nascimento Jéssica Tauany Andrade Letícia Vieira Rosy Iara Maciel de Azambuja Ribeiro Ralph Gruppi Thomé Hélio Batista dos Santos Jaqueline Maria Siqueira Ferreira Adriana Cristina Soares |
author_sort |
William Gustavo Lima |
title |
Are the Statins promising antifungal agents against invasive candidiasis? |
title_short |
Are the Statins promising antifungal agents against invasive candidiasis? |
title_full |
Are the Statins promising antifungal agents against invasive candidiasis? |
title_fullStr |
Are the Statins promising antifungal agents against invasive candidiasis? |
title_full_unstemmed |
Are the Statins promising antifungal agents against invasive candidiasis? |
title_sort |
are the statins promising antifungal agents against invasive candidiasis? |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-03-01 |
description |
The medical importance of intra-abdominal candidiasis (IAC) contrasts with the limited number of pharmacological treatment options available and the increasing rate of resistance to antifungal drugs. Thus, the repositioning of compounds in clinical use can contribute to the broadening of treatment possibilities for this infection. Statins, a class of drugs used to reduce cardiovascular event risk, have shown antiparasitic, antibacterial, and antiviral activities; however, their antifungal effects remain poorly studied. In this context, the present study aimed to elucidate the antifungal potential of six statins in vitro, as well as to evaluate the therapeutic use of fluvastatin in a mouse model of IAC. The biological effects of statins were evaluated against Candida spp., through the determination of the minimum inhibitory concentration (MIC). For the statins that showed activity, the fungicidal concentration, toxicity/selectivity, synergism with azoles and polyenes, phenotypic effects, and activity against virulence factors were also determined. Atorvastatin, rosuvastatin and fluvastatin were highly active, especially against C. albicans (MIC < 1–128 μg.mL−1) and C. glabrata (MIC 32–64 μg.mL−1). Fluvastatin and atorvastatin were selective for C. albicans in baby hamster kidney (BHK) cells. Moreover, all active statins in the antifungal assay showed high selectivity for fungal cells over bacteria. The combination of atorvastatin, rosuvastatin, and fluvastatin with azoles was associated with a synergistic effect. Active statins do not act on the fungal membrane or wall, but instead stimulate farnesol-dependent pathogenicity factors such as yeast-to-hyphal transition and biofilm generation. Fluvastatin treatment was evaluated in a mouse model of IAC, showing stimulation of the extra-hepatic dissemination of C. albicans but improvements in renal, splenic, and hepatic histological aspects. In conclusion, statins have potent antifungal activity in vitro, but the therapeutic effect in vivo is restricted to their anti-inflammatory activity. |
topic |
Candida albicans Biofilm Yeast-to-hyphal transition Synergism Fluvastatin Intra-abdominal candidiasis |
url |
http://www.sciencedirect.com/science/article/pii/S0753332218346602 |
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doaj-ef392a07bdbf43908e95bd70c1e6ab0e2021-05-20T07:35:29ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-03-01111270281Are the Statins promising antifungal agents against invasive candidiasis?William Gustavo Lima0Lídia Anita Alves-Nascimento1Jéssica Tauany Andrade2Letícia Vieira3Rosy Iara Maciel de Azambuja Ribeiro4Ralph Gruppi Thomé5Hélio Batista dos Santos6Jaqueline Maria Siqueira Ferreira7Adriana Cristina Soares8Laboratório de Microbiologia Médica, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, Brazil; Laboratório de Farmacologia da Dor e Inflamação, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, Brazil; Corresponding author at: Laboratório de Farmacologia da Dor e Inflamação, Universidade Federal de São João Del-Rei, Campus Centro-Oeste Dona Lindu, Rua Sebastião Gonçalves Coelho, no 400, Chanadour, Divinópolis, Minas Gerais, CEP: 35501-293, Brazil.Laboratório de Microbiologia Médica, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilLaboratório de Microbiologia Médica, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilLaboratório de Farmacologia da Dor e Inflamação, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, Brazil; Laboratório de Processamento de Tecidos, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilLaboratório de Patologia Experimental, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilLaboratório de Processamento de Tecidos, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilLaboratório de Processamento de Tecidos, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilLaboratório de Microbiologia Médica, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilLaboratório de Farmacologia da Dor e Inflamação, Universidade Federal de São João del-Rei (UFSJ), Campus Centro-Oeste Dona Lindu, Divinópolis, Minas Gerais, BrazilThe medical importance of intra-abdominal candidiasis (IAC) contrasts with the limited number of pharmacological treatment options available and the increasing rate of resistance to antifungal drugs. Thus, the repositioning of compounds in clinical use can contribute to the broadening of treatment possibilities for this infection. Statins, a class of drugs used to reduce cardiovascular event risk, have shown antiparasitic, antibacterial, and antiviral activities; however, their antifungal effects remain poorly studied. In this context, the present study aimed to elucidate the antifungal potential of six statins in vitro, as well as to evaluate the therapeutic use of fluvastatin in a mouse model of IAC. The biological effects of statins were evaluated against Candida spp., through the determination of the minimum inhibitory concentration (MIC). For the statins that showed activity, the fungicidal concentration, toxicity/selectivity, synergism with azoles and polyenes, phenotypic effects, and activity against virulence factors were also determined. Atorvastatin, rosuvastatin and fluvastatin were highly active, especially against C. albicans (MIC < 1–128 μg.mL−1) and C. glabrata (MIC 32–64 μg.mL−1). Fluvastatin and atorvastatin were selective for C. albicans in baby hamster kidney (BHK) cells. Moreover, all active statins in the antifungal assay showed high selectivity for fungal cells over bacteria. The combination of atorvastatin, rosuvastatin, and fluvastatin with azoles was associated with a synergistic effect. Active statins do not act on the fungal membrane or wall, but instead stimulate farnesol-dependent pathogenicity factors such as yeast-to-hyphal transition and biofilm generation. Fluvastatin treatment was evaluated in a mouse model of IAC, showing stimulation of the extra-hepatic dissemination of C. albicans but improvements in renal, splenic, and hepatic histological aspects. In conclusion, statins have potent antifungal activity in vitro, but the therapeutic effect in vivo is restricted to their anti-inflammatory activity.http://www.sciencedirect.com/science/article/pii/S0753332218346602Candida albicansBiofilmYeast-to-hyphal transitionSynergismFluvastatinIntra-abdominal candidiasis |