Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1080/21505594.2020.1868814 http://hdl.handle.net/11449/208309 |
Resumo: | The emergence of resistance requires alternative methods to treat Candida albicans infections. We evaluated efficacy of the efflux pump inhibitor (EPI) verapamil (VER) with fluconazole (FLC) against FLC-resistant (CaR) and -susceptible C. albicans (CaS). The susceptibility of both strains to VER and FLC was determined, as well as the synergism of VER with FLC. Experiments were performed in vitro for planktonic cultures and biofilms and in vivo using Galleria mellonella. Larval survival and fungal recovery were evaluated after treatment with VER and FLC. Data were analyzed by analysis of variance and Kaplan-Meier tests. The combination of VER with FLC at sub-lethal concentrations reduced fungal growth. VER inhibited the efflux of rhodamine 123 and showed synergism with FLC against CaR. For biofilms, FLC and VER alone reduced fungal viability. The combination of VER with FLC at sub-lethal concentrations also reduced biofilm viability. In the in vivo assays, VER and FLC used alone or in combination increased the survival of larvae infected with CaR. Reduction of fungal recovery was observed only for larvae infected with CaR and treated with VER with FLC. VER reverted the FLC-resistance of C. albicans. Based on the results obtained, VER reverted the FLC-resistance of C. albicans and showed synergism with FLC against CaR. VER also increased the survival of G. mellonella infected with CaR and reduced the fungal recovery. |
id |
UNSP_2f55a1a1f4b094310b1d0260b560e7ab |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/208309 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonellaCandida albicansdrug resistanceGalleria mellonellamembrane transport proteinsvirulenceThe emergence of resistance requires alternative methods to treat Candida albicans infections. We evaluated efficacy of the efflux pump inhibitor (EPI) verapamil (VER) with fluconazole (FLC) against FLC-resistant (CaR) and -susceptible C. albicans (CaS). The susceptibility of both strains to VER and FLC was determined, as well as the synergism of VER with FLC. Experiments were performed in vitro for planktonic cultures and biofilms and in vivo using Galleria mellonella. Larval survival and fungal recovery were evaluated after treatment with VER and FLC. Data were analyzed by analysis of variance and Kaplan-Meier tests. The combination of VER with FLC at sub-lethal concentrations reduced fungal growth. VER inhibited the efflux of rhodamine 123 and showed synergism with FLC against CaR. For biofilms, FLC and VER alone reduced fungal viability. The combination of VER with FLC at sub-lethal concentrations also reduced biofilm viability. In the in vivo assays, VER and FLC used alone or in combination increased the survival of larvae infected with CaR. Reduction of fungal recovery was observed only for larvae infected with CaR and treated with VER with FLC. VER reverted the FLC-resistance of C. albicans. Based on the results obtained, VER reverted the FLC-resistance of C. albicans and showed synergism with FLC against CaR. VER also increased the survival of G. mellonella infected with CaR and reduced the fungal recovery.Laboratory of Applied Microbiology Department of Dental Materials and Prosthodontics São Paulo State University (UNESP) School of DentistryFaculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo (USP)Laboratory of Applied Microbiology Department of Dental Materials and Prosthodontics São Paulo State University (UNESP) School of DentistryUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Vega-Chacón, Yuliana [UNESP]de Albuquerque, Maria Carolina [UNESP]Pavarina, Ana Cláudia [UNESP]Goldman, Gustavo HenriqueMima, Ewerton Garcia de Oliveira [UNESP]2021-06-25T11:10:06Z2021-06-25T11:10:06Z2021-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article231-243http://dx.doi.org/10.1080/21505594.2020.1868814Virulence, v. 12, n. 1, p. 231-243, 2021.2150-56082150-5594http://hdl.handle.net/11449/20830910.1080/21505594.2020.18688142-s2.0-85099175905Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengVirulenceinfo:eu-repo/semantics/openAccess2021-10-23T19:01:58Zoai:repositorio.unesp.br:11449/208309Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T19:01:58Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella |
title |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella |
spellingShingle |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella Vega-Chacón, Yuliana [UNESP] Candida albicans drug resistance Galleria mellonella membrane transport proteins virulence |
title_short |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella |
title_full |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella |
title_fullStr |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella |
title_full_unstemmed |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella |
title_sort |
Verapamil inhibits efflux pumps in Candida albicans, exhibits synergism with fluconazole, and increases survival of Galleria mellonella |
author |
Vega-Chacón, Yuliana [UNESP] |
author_facet |
Vega-Chacón, Yuliana [UNESP] de Albuquerque, Maria Carolina [UNESP] Pavarina, Ana Cláudia [UNESP] Goldman, Gustavo Henrique Mima, Ewerton Garcia de Oliveira [UNESP] |
author_role |
author |
author2 |
de Albuquerque, Maria Carolina [UNESP] Pavarina, Ana Cláudia [UNESP] Goldman, Gustavo Henrique Mima, Ewerton Garcia de Oliveira [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Vega-Chacón, Yuliana [UNESP] de Albuquerque, Maria Carolina [UNESP] Pavarina, Ana Cláudia [UNESP] Goldman, Gustavo Henrique Mima, Ewerton Garcia de Oliveira [UNESP] |
dc.subject.por.fl_str_mv |
Candida albicans drug resistance Galleria mellonella membrane transport proteins virulence |
topic |
Candida albicans drug resistance Galleria mellonella membrane transport proteins virulence |
description |
The emergence of resistance requires alternative methods to treat Candida albicans infections. We evaluated efficacy of the efflux pump inhibitor (EPI) verapamil (VER) with fluconazole (FLC) against FLC-resistant (CaR) and -susceptible C. albicans (CaS). The susceptibility of both strains to VER and FLC was determined, as well as the synergism of VER with FLC. Experiments were performed in vitro for planktonic cultures and biofilms and in vivo using Galleria mellonella. Larval survival and fungal recovery were evaluated after treatment with VER and FLC. Data were analyzed by analysis of variance and Kaplan-Meier tests. The combination of VER with FLC at sub-lethal concentrations reduced fungal growth. VER inhibited the efflux of rhodamine 123 and showed synergism with FLC against CaR. For biofilms, FLC and VER alone reduced fungal viability. The combination of VER with FLC at sub-lethal concentrations also reduced biofilm viability. In the in vivo assays, VER and FLC used alone or in combination increased the survival of larvae infected with CaR. Reduction of fungal recovery was observed only for larvae infected with CaR and treated with VER with FLC. VER reverted the FLC-resistance of C. albicans. Based on the results obtained, VER reverted the FLC-resistance of C. albicans and showed synergism with FLC against CaR. VER also increased the survival of G. mellonella infected with CaR and reduced the fungal recovery. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T11:10:06Z 2021-06-25T11:10:06Z 2021-01-01 |
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/10.1080/21505594.2020.1868814 Virulence, v. 12, n. 1, p. 231-243, 2021. 2150-5608 2150-5594 http://hdl.handle.net/11449/208309 10.1080/21505594.2020.1868814 2-s2.0-85099175905 |
url |
http://dx.doi.org/10.1080/21505594.2020.1868814 http://hdl.handle.net/11449/208309 |
identifier_str_mv |
Virulence, v. 12, n. 1, p. 231-243, 2021. 2150-5608 2150-5594 10.1080/21505594.2020.1868814 2-s2.0-85099175905 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Virulence |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
231-243 |
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 |
|
_version_ |
1797789689421234176 |