Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1

Background: The development of multidrug resistance (MDR) associated with the overexpression of the efflux transporters Mdr1 and Cdr1 in Candida species impedes antifungal therapies. The urgent need for novel agents able to inhibit the function of both pumps, led us to evaluate this property in 137...

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Autores principales: Gil, Florimar, Laiolo, Jerónimo, Bayona-Pacheco, Brayan, Cannon, Richard D.
Formato: Artículo
Lenguaje:Español
Publicado: BioMed Central Ltd 2022
Materias:
R Medicina (General)
RM Terapéutica. Farmacología
Acceso en línea:http://pa.bibdigital.ucc.edu.ar/3451/1/A_Gil_Laiolo_Bayona-Pacheco.pdf
Aporte de:
Producción Académica Universidad Católica de Córdoba (UCCor) de Universidad Católica de Córdoba
id I38-R144-3451
record_format dspace
spelling I38-R144-34512025-04-10T18:33:42Z http://pa.bibdigital.ucc.edu.ar/3451/ Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1 Gil, Florimar Laiolo, Jerónimo Bayona-Pacheco, Brayan Cannon, Richard D. R Medicina (General) RM Terapéutica. Farmacología Background: The development of multidrug resistance (MDR) associated with the overexpression of the efflux transporters Mdr1 and Cdr1 in Candida species impedes antifungal therapies. The urgent need for novel agents able to inhibit the function of both pumps, led us to evaluate this property in 137 extracts obtained from Argentinian plants. Methods: The ability of the extracts to reverse efflux pump-mediated MDR was determined with an agar chemosensitization assay using fluconazole (FCZ) resistant Mdr1- and Cdr1-overexpressing clinical isolates of Candida albicans and Candida glabrata as well as Saccharomyces cerevisiae strains selectively expressing Mdr1 (AD/CaMDR1) or Cdr1 (AD/CaCDR1). The resistance-reversing activity of the most potent extracts was further confirmed using a Nile Red accumulation assay. Results: Fifteen plant extracts overcame the FCZ resistance of Candida albicans 1114, which overexpresses CaMdr1 and CaCdr1, and AD/CaMDR1, with those from Acalypha communis and Solanum atriplicifolium being the most effective showing 4- to 16-fold reversal of resistance at concentrations ≥ 25 µg/mL. Both extracts, and to a lesser extent that from Pterocaulon alopecuroides, also restored FCZ sensitivity in CgCdr1-overexpressing C. glabrata 109 and in AD/CaCDR1 with fold reversal values ranging from 4 to 32 and therefore demonstrating a dual effect against Mdr1 and Cdr1. Both, A. communis and S. atriplicifolium extracts at concentrations ≥ 12.5 and ≥ 25 µg/mL, respectively, increased the intracellular Nile Red accumulation in all yeast strains overexpressing efflux pumps. Conclusions: The non-toxic and highly active extracts from A. communis and S. atripicifolium, provide promising sources of compounds for potentiating the antifungal effect of FCZ by blocking the efflux function of Mdr1 and Cdr1 transporters. BioMed Central Ltd 2022-12 info:eu-repo/semantics/article info:eu-repo/semantics/closedAccess application/pdf spa http://pa.bibdigital.ucc.edu.ar/3451/1/A_Gil_Laiolo_Bayona-Pacheco.pdf Gil, Florimar, Laiolo, Jerónimo ORCID: https://orcid.org/0000-0001-8971-9684 <https://orcid.org/0000-0001-8971-9684>, Bayona-Pacheco, Brayan and Cannon, Richard D. ORCID: https://orcid.org/0000-0002-5398-2066 <https://orcid.org/0000-0002-5398-2066> (2022) Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1. BMC Complementary Medicine and Therapies, 22 (1). ISSN 2662-7671 https://www.scopus.com/redirect/linking.uri?targetURL=https%3a%2f%2fdoi.org%2f10.1186%2fs12906-022-03745-4&locationID=1&categoryID=4&eid=2-s2.0-85139766111&issn=26627671&linkType=ViewAtPublisher&year=2022&origin=recordpage&dig=91a64a37a6220f2092d11d2912160a7a info:eu-repo/semantics/altIdentifier/doi/10.1186/s12906-022-03745-4
institution Universidad Católica de Córdoba
institution_str I-38
repository_str R-144
collection Producción Académica Universidad Católica de Córdoba (UCCor)
language Español
orig_language_str_mv spa
topic R Medicina (General)
RM Terapéutica. Farmacología
spellingShingle R Medicina (General)
RM Terapéutica. Farmacología
Gil, Florimar
Laiolo, Jerónimo
Bayona-Pacheco, Brayan
Cannon, Richard D.
Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1
topic_facet R Medicina (General)
RM Terapéutica. Farmacología
description Background: The development of multidrug resistance (MDR) associated with the overexpression of the efflux transporters Mdr1 and Cdr1 in Candida species impedes antifungal therapies. The urgent need for novel agents able to inhibit the function of both pumps, led us to evaluate this property in 137 extracts obtained from Argentinian plants. Methods: The ability of the extracts to reverse efflux pump-mediated MDR was determined with an agar chemosensitization assay using fluconazole (FCZ) resistant Mdr1- and Cdr1-overexpressing clinical isolates of Candida albicans and Candida glabrata as well as Saccharomyces cerevisiae strains selectively expressing Mdr1 (AD/CaMDR1) or Cdr1 (AD/CaCDR1). The resistance-reversing activity of the most potent extracts was further confirmed using a Nile Red accumulation assay. Results: Fifteen plant extracts overcame the FCZ resistance of Candida albicans 1114, which overexpresses CaMdr1 and CaCdr1, and AD/CaMDR1, with those from Acalypha communis and Solanum atriplicifolium being the most effective showing 4- to 16-fold reversal of resistance at concentrations ≥ 25 µg/mL. Both extracts, and to a lesser extent that from Pterocaulon alopecuroides, also restored FCZ sensitivity in CgCdr1-overexpressing C. glabrata 109 and in AD/CaCDR1 with fold reversal values ranging from 4 to 32 and therefore demonstrating a dual effect against Mdr1 and Cdr1. Both, A. communis and S. atriplicifolium extracts at concentrations ≥ 12.5 and ≥ 25 µg/mL, respectively, increased the intracellular Nile Red accumulation in all yeast strains overexpressing efflux pumps. Conclusions: The non-toxic and highly active extracts from A. communis and S. atripicifolium, provide promising sources of compounds for potentiating the antifungal effect of FCZ by blocking the efflux function of Mdr1 and Cdr1 transporters.
format Artículo
author Gil, Florimar
Laiolo, Jerónimo
Bayona-Pacheco, Brayan
Cannon, Richard D.
author_facet Gil, Florimar
Laiolo, Jerónimo
Bayona-Pacheco, Brayan
Cannon, Richard D.
author_sort Gil, Florimar
title Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1
title_short Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1
title_full Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1
title_fullStr Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1
title_full_unstemmed Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1
title_sort extracts from argentinian native plants reverse fluconazole resistance in candida species by inhibiting the efflux transporters mdr1 and cdr1
publisher BioMed Central Ltd
publishDate 2022
url http://pa.bibdigital.ucc.edu.ar/3451/1/A_Gil_Laiolo_Bayona-Pacheco.pdf
work_keys_str_mv AT gilflorimar extractsfromargentiniannativeplantsreversefluconazoleresistanceincandidaspeciesbyinhibitingtheeffluxtransportersmdr1andcdr1
AT laiolojeronimo extractsfromargentiniannativeplantsreversefluconazoleresistanceincandidaspeciesbyinhibitingtheeffluxtransportersmdr1andcdr1
AT bayonapachecobrayan extractsfromargentiniannativeplantsreversefluconazoleresistanceincandidaspeciesbyinhibitingtheeffluxtransportersmdr1andcdr1
AT cannonrichardd extractsfromargentiniannativeplantsreversefluconazoleresistanceincandidaspeciesbyinhibitingtheeffluxtransportersmdr1andcdr1
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