Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model

The multidrug-resistant Candida auris is a global health emergency, being responsible for outbreaks of invasive candidiasis worldwide. Limited effective therapeutic options make it difficult to treat this emerging pathogen. In this context, combinations of different antifungal drugs are considered a...

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Autores: Hernando Ortiz, Ainara, Eraso, Elena, Jauregizar, Nerea, de Groot, Petrus Wilhelmus Johannes, Quindós, Guillermo, Mateo, Estibáliz
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/47053
Acceso en línea:https://journals.asm.org/doi/full/10.1128/spectrum.02086-23
https://hdl.handle.net/10578/47053
Access Level:acceso abierto
Palabra clave:Amphotericin B
Antifungal activity
Caenorhabditis elegans model
Candida auris
Candidiasis
Drug combinations
Echinocandins
Synergy
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spelling Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host modelHernando Ortiz, AinaraEraso, ElenaJauregizar, Nereade Groot, Petrus Wilhelmus JohannesQuindós, GuillermoMateo, EstibálizAmphotericin BAntifungal activityCaenorhabditis elegans modelCandida aurisCandidiasisDrug combinationsEchinocandinsSynergyThe multidrug-resistant Candida auris is a global health emergency, being responsible for outbreaks of invasive candidiasis worldwide. Limited effective therapeutic options make it difficult to treat this emerging pathogen. In this context, combinations of different antifungal drugs are considered a promising therapeutic alternative. The aim of this work was to analyze the antifungal activity of combinations of amphotericin B and echinocandins against five clinical blood isolates of C. auris. One of these isolates showed an aggregative phenotype already described in C. auris species, forming large aggregates of cells that are very difficult to disintegrate. First, the in vitro activity of these drugs was evaluated both in monotherapy and in combination, and results showed synergistic interactions between amphotericin B and echinocandins in most cases, although higher minimum inhibitory concentration (MIC) values were observed against the aggregative isolate compared to non-aggregative counterparts. The most promising drug combinations were then selected for in vivo activity evaluation using a Caenorhabditis elegans model of candidiasis and by determination of survival rates. The combination of amphotericin B and caspofungin showed the strongest protective effect during C. elegans infection with C. auris blood isolates, achieving up to 99% C. elegans survival. Although the MIC values for micafungin were low in vitro, these drug concentrations had no effect in vivo, and the combination of amphotericin B and micafungin was the least effective. The results of this study showed that the combination amphotericin B and echinocandins might be a promising therapeutic approach for the treatment of invasive candidiasis caused by C. auris. Moreover, the nematode C. elegans is a suitable alternative model for screening of new therapeutic agents capable of overcoming multidrug-resistant C. auris infections. IMPORTANCEMultidrug resistance is a rising problem among non-Candida albicans species, such as Candida auris. This therapeutic problem has been very important during the COVID-19 pandemic. The World Health Organization has included C. auris in its global priority list of health-threatening fungi, to study this emerging multidrug-resistant species and to develop effective alternative therapies. In the present study, the synergistic effect of the combination of amphotericin B and echinocandins has been demonstrated against blood isolates of C. auris. Different susceptibility responses were also observed between aggregative and non-aggregative phenotypes. The antifungal activity of these drug combinations against C. auris was also demonstrated in the Caenorhabditis elegans host model of candidiasis, confirming the suitability and usefulness of this model in the search for solutions to antimicrobial resistance.American Society for Microbiology202620262024info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://journals.asm.org/doi/full/10.1128/spectrum.02086-23https://hdl.handle.net/10578/47053reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésPID2020-117983RB-I00IT1607-22PIF 16/39info:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/470532026-05-27T07:36:41Z
dc.title.none.fl_str_mv Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
title Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
spellingShingle Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
Hernando Ortiz, Ainara
Amphotericin B
Antifungal activity
Caenorhabditis elegans model
Candida auris
Candidiasis
Drug combinations
Echinocandins
Synergy
title_short Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
title_full Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
title_fullStr Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
title_full_unstemmed Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
title_sort Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model
dc.creator.none.fl_str_mv Hernando Ortiz, Ainara
Eraso, Elena
Jauregizar, Nerea
de Groot, Petrus Wilhelmus Johannes
Quindós, Guillermo
Mateo, Estibáliz
author Hernando Ortiz, Ainara
author_facet Hernando Ortiz, Ainara
Eraso, Elena
Jauregizar, Nerea
de Groot, Petrus Wilhelmus Johannes
Quindós, Guillermo
Mateo, Estibáliz
author_role author
author2 Eraso, Elena
Jauregizar, Nerea
de Groot, Petrus Wilhelmus Johannes
Quindós, Guillermo
Mateo, Estibáliz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Amphotericin B
Antifungal activity
Caenorhabditis elegans model
Candida auris
Candidiasis
Drug combinations
Echinocandins
Synergy
topic Amphotericin B
Antifungal activity
Caenorhabditis elegans model
Candida auris
Candidiasis
Drug combinations
Echinocandins
Synergy
description The multidrug-resistant Candida auris is a global health emergency, being responsible for outbreaks of invasive candidiasis worldwide. Limited effective therapeutic options make it difficult to treat this emerging pathogen. In this context, combinations of different antifungal drugs are considered a promising therapeutic alternative. The aim of this work was to analyze the antifungal activity of combinations of amphotericin B and echinocandins against five clinical blood isolates of C. auris. One of these isolates showed an aggregative phenotype already described in C. auris species, forming large aggregates of cells that are very difficult to disintegrate. First, the in vitro activity of these drugs was evaluated both in monotherapy and in combination, and results showed synergistic interactions between amphotericin B and echinocandins in most cases, although higher minimum inhibitory concentration (MIC) values were observed against the aggregative isolate compared to non-aggregative counterparts. The most promising drug combinations were then selected for in vivo activity evaluation using a Caenorhabditis elegans model of candidiasis and by determination of survival rates. The combination of amphotericin B and caspofungin showed the strongest protective effect during C. elegans infection with C. auris blood isolates, achieving up to 99% C. elegans survival. Although the MIC values for micafungin were low in vitro, these drug concentrations had no effect in vivo, and the combination of amphotericin B and micafungin was the least effective. The results of this study showed that the combination amphotericin B and echinocandins might be a promising therapeutic approach for the treatment of invasive candidiasis caused by C. auris. Moreover, the nematode C. elegans is a suitable alternative model for screening of new therapeutic agents capable of overcoming multidrug-resistant C. auris infections. IMPORTANCEMultidrug resistance is a rising problem among non-Candida albicans species, such as Candida auris. This therapeutic problem has been very important during the COVID-19 pandemic. The World Health Organization has included C. auris in its global priority list of health-threatening fungi, to study this emerging multidrug-resistant species and to develop effective alternative therapies. In the present study, the synergistic effect of the combination of amphotericin B and echinocandins has been demonstrated against blood isolates of C. auris. Different susceptibility responses were also observed between aggregative and non-aggregative phenotypes. The antifungal activity of these drug combinations against C. auris was also demonstrated in the Caenorhabditis elegans host model of candidiasis, confirming the suitability and usefulness of this model in the search for solutions to antimicrobial resistance.
publishDate 2024
dc.date.none.fl_str_mv 2024
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://journals.asm.org/doi/full/10.1128/spectrum.02086-23
https://hdl.handle.net/10578/47053
url https://journals.asm.org/doi/full/10.1128/spectrum.02086-23
https://hdl.handle.net/10578/47053
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PID2020-117983RB-I00
IT1607-22
PIF 16/39
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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