Rational selection of morphological phenotypic traits to extract essential similarities in chemical perturbation in the ergosterol pathway.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 08 2024
06 08 2024
Historique:
received:
07
02
2024
accepted:
15
07
2024
medline:
7
8
2024
pubmed:
7
8
2024
entrez:
6
8
2024
Statut:
epublish
Résumé
Terbinafine, fluconazole, and amorolfine inhibit fungal ergosterol synthesis by acting on their target enzymes at different steps in the synthetic pathway, causing the accumulation of various intermediates. We found that the effects of these three in- hibitors on yeast morphology were different. The number of morphological parameters commonly altered by these drugs was only approximately 6% of the total. Using a rational strategy to find commonly changed parameters,we focused on hidden essential similarities in the phenotypes possibly due to decreased ergosterol levels. This resulted in higher apparent morphological similarity. Improvements in morphological similarity were observed even when canonical correlation analysis was used to select biologically meaningful morphological parameters related to gene function. In addition to changes in cell morphology, we also observed differences in the synergistic effects among the three inhibitors and in their fungicidal effects against pathogenic fungi possibly due to the accumulation of different intermediates. This study provided a comprehensive understanding of the properties of inhibitors acting in the same biosynthetic pathway.
Identifiants
pubmed: 39107358
doi: 10.1038/s41598-024-67634-1
pii: 10.1038/s41598-024-67634-1
doi:
Substances chimiques
Ergosterol
Z30RAY509F
Antifungal Agents
0
Fluconazole
8VZV102JFY
Terbinafine
G7RIW8S0XP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17093Subventions
Organisme : Japan Society for the Promotion of Science
ID : 23K23483
Informations de copyright
© 2024. The Author(s).
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