Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Caldara, Marina, Marmiroli, Nelson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783544551233814528
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
work_keys_str_mv AT caldaramarina knownantimicrobialsversusnortriptylineincandidaalbicansrepositioninganolddrugfornewtargets
AT marmirolinelson knownantimicrobialsversusnortriptylineincandidaalbicansrepositioninganolddrugfornewtargets