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Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets
Candida albicans has the capacity to develop resistance to commonly used antimicrobials, and to solve this problem, drug repositioning and new drug combinations are being studied. Nortriptyline, a tricyclic antidepressant, was shown to have the capacity to inhibit biofilm and hyphae formation, along...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284794/ https://www.ncbi.nlm.nih.gov/pubmed/32429222 http://dx.doi.org/10.3390/microorganisms8050742 |
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author | Caldara, Marina Marmiroli, Nelson |
author_facet | Caldara, Marina Marmiroli, Nelson |
author_sort | Caldara, Marina |
collection | PubMed |
description | Candida albicans has the capacity to develop resistance to commonly used antimicrobials, and to solve this problem, drug repositioning and new drug combinations are being studied. Nortriptyline, a tricyclic antidepressant, was shown to have the capacity to inhibit biofilm and hyphae formation, along with the ability to efficiently kill cells in a mature biofilm. To use nortriptyline as a new antimicrobial, or in combination with known drugs to increase their actions, it is important to characterize in more detail the effects of this drug on the target species. In this study, the Candida albicans GRACE™ collection and a Haplo insufficiency profiling were employed to identify the potential targets of nortriptyline, and to classify, in a parallel screening with amphotericin B, caspofungin, and fluconazole, general multi-drug resistance genes. The results identified mutants that, during biofilm formation and upon treatment of a mature biofilm, are sensitive or tolerant to nortriptyline, or to general drug treatments. Gene ontology analysis recognized the categories of ribosome biogenesis and spliceosome as enriched upon treatment with the tricyclic antidepressant, while mutants in oxidative stress response and general stress response were commonly retrieved upon treatment with any other drug. The data presented suggest that nortriptyline can be considered a “new” antimicrobial drug with large potential for application to in vivo infection models. |
format | Online Article Text |
id | pubmed-7284794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72847942020-06-15 Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets Caldara, Marina Marmiroli, Nelson Microorganisms Article Candida albicans has the capacity to develop resistance to commonly used antimicrobials, and to solve this problem, drug repositioning and new drug combinations are being studied. Nortriptyline, a tricyclic antidepressant, was shown to have the capacity to inhibit biofilm and hyphae formation, along with the ability to efficiently kill cells in a mature biofilm. To use nortriptyline as a new antimicrobial, or in combination with known drugs to increase their actions, it is important to characterize in more detail the effects of this drug on the target species. In this study, the Candida albicans GRACE™ collection and a Haplo insufficiency profiling were employed to identify the potential targets of nortriptyline, and to classify, in a parallel screening with amphotericin B, caspofungin, and fluconazole, general multi-drug resistance genes. The results identified mutants that, during biofilm formation and upon treatment of a mature biofilm, are sensitive or tolerant to nortriptyline, or to general drug treatments. Gene ontology analysis recognized the categories of ribosome biogenesis and spliceosome as enriched upon treatment with the tricyclic antidepressant, while mutants in oxidative stress response and general stress response were commonly retrieved upon treatment with any other drug. The data presented suggest that nortriptyline can be considered a “new” antimicrobial drug with large potential for application to in vivo infection models. MDPI 2020-05-15 /pmc/articles/PMC7284794/ /pubmed/32429222 http://dx.doi.org/10.3390/microorganisms8050742 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Caldara, Marina Marmiroli, Nelson Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets |
title | Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets |
title_full | Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets |
title_fullStr | Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets |
title_full_unstemmed | Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets |
title_short | Known Antimicrobials Versus Nortriptyline in Candida albicans: Repositioning an Old Drug for New Targets |
title_sort | known antimicrobials versus nortriptyline in candida albicans: repositioning an old drug for new targets |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284794/ https://www.ncbi.nlm.nih.gov/pubmed/32429222 http://dx.doi.org/10.3390/microorganisms8050742 |
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