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Identification of efflux inhibitors through a drug repurposing strategy in Candida albicans

2026-05-18Artigo científico Acesso aberto
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dc.contributor.authorMarques, Débora
dc.contributor.authorCosta, Sofia Santos
dc.contributor.authorRodrigues, Liliana
dc.contributor.institutionLaboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.institutionTB, HIV and opportunistic diseases and pathogens (THOP)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.pblFrontiers Media
dc.date.accessioned2026-06-21T14:45:01Z
dc.date.available2026-06-21T14:45:01Z
dc.date.issued2026-05-18
dc.descriptionFunding information: The author(s) declared that financial support was received for this work and/or its publication. This work is funded by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., under the R&D unit Global Health and Tropical Medicine (UID/04413/2025) and the Associated Laboratory in Translation and Innovation Towards Global Health REAL (LA/P/0117/2020). Additional support was provided by the DrugsForNg project Ref. UID/04413/2020 – DrugsForNg, and the DREBI Project Ref. 2022.07931.PTDC (doi: 10.54499/2022.07931.PTDC). Publisher Copyright: Copyright © 2026 Marques, Costa and Rodrigues.
dc.description.abstractIntroduction – Candida albicans is a major cause of nosocomial fungal infections, often associated with high morbidity and mortality. The rising resistance to antifungal drugs, particularly azoles, underscores the need for new therapeutic strategies. Among resistance mechanisms, alterations in drug targets and overexpression of efflux pump genes play key roles. Efflux inhibitors can enhance the intracellular drug accumulation, thereby restoring antifungal efficacy and preventing resistance development. Drug repurposing offers a cost-effective and time-efficient alternative for identifying new drugs, including efflux inhibitors. In this study, we used an in silico drug repurposing approach to identify approved drugs associated with membrane transport functions and evaluate their efflux-modulating potential in vitro. Methods – Using the DrugBank database, we screened predicted membrane transport proteins in C. albicans and selected those with homology to known drug targets. A subset of drugs, representative of each chemical group, was selected for in vitro screening against the reference strain C. albicans ATCC 90028. We further evaluated the potential adjuvant effect of these drugs on the activity of fluconazole. Finally, the efflux inhibitory effect of the candidate drugs was assessed by real-time fluorometric detection of ethidium bromide accumulation. Results – A total of 245 predicted membrane transport proteins were screened, 51 of which showed homology to known drug targets and were associated with 777 drugs. A subset of 59 drugs was selected for screening. The drug miltefosine showed the lowest minimum inhibitory concentration (MIC; 2 mg/L), while amlodipine and procainamide demonstrated an adjuvant effect by decreasing the MIC of fluconazole by at least four-fold. Fluorometric assays revealed amlodipine, fluvoxamine and fluoxetine as potential efflux inhibitors in C. albicans. Discussion – These findings highlight the potential of these drugs to contribute to the research and development of new therapeutic alternatives aimed at combating antifungal resistance.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent3586006
dc.identifier.doi10.3389/fcimb.2026.1798450
dc.identifier.issn2235-2988
dc.identifier.otherPURE: 165023628
dc.identifier.otherPURE UUID: 960a040b-c415-4fab-9492-2bfe9ed8984c
dc.identifier.otherScopus: 105041175082
dc.identifier.otherWOS: 001780334500001
dc.identifier.otherPubMed: 42233159
dc.identifier.otherPubMedCentral: PMC13222938
dc.identifier.otherORCID: /0000-0002-4096-2410/work/218363972
dc.identifier.otherORCID: /0000-0002-2094-2666/work/218364074
dc.identifier.urihttp://hdl.handle.net/10362/203943
dc.identifier.urlhttps://www.scopus.com/pages/publications/105041175082
dc.language.isoeng
dc.peerreviewedyes
dc.subjectCandida albicans
dc.subjectdrug repurposing
dc.subjectefflux inhibitors
dc.subjectefflux pumps
dc.subjectphenotypic screening
dc.subjectMicrobiology
dc.subjectImmunology
dc.subjectMicrobiology (medical)
dc.subjectInfectious Diseases
dc.subjectSDG 3 - Good Health and Well-being
dc.titleIdentification of efflux inhibitors through a drug repurposing strategy in Candida albicansen
dc.typejournal article
degois.publication.titleFrontiers in Cellular and Infection Microbiology
degois.publication.volume16
dspace.entity.typePublication
rcaap.rightsopenAccess

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