ArticleApplied and environmental microbiology2014
Clotrimazole as a potent agent for treating the oomycete fish pathogen Saprolegnia parasitica through inhibition of sterol 14α-demethylase (CYP51).
Article in Applied and environmental microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Immune-pathological response induced by Saprolegnia parasitica in Pangasianodon hypophthalmus and assessment of clinical efficacy of clotrimazole.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026Article
- Parasitisterols A-C, 24,25-Dihydroxycholestane-Type Triterpenoids, from Oomycete Fish PathogenACS omega · 2026Article
- Population pharmacokinetics, in-feed bioavailability and tissue depletion of imidazole antifungal clotrimazole in Pangasianodon hypophthalmus.Veterinary research communications · 2026Article
- Abiotic stressors influence saprolegniasis infection, causing mass mortality in Pangasianodon hypophthalmus and Labeo rohita under cage culture in Eastern India.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Metatranscriptomes-based sequence similarity networks uncover genetic signatures within parasitic freshwater microbial eukaryotes.Microbiome · 2025Article
- Isolation and characterization of Saprolegnia parasitica from cage-reared Pangasianodon hypophthalmus and its sensitivity to different antifungal compounds.Scientific reports · 2024Article
- Loss of Sterol Biosynthesis in Economically Important Plant Pests and Pathogens: A Review of a Potential Target for Pest Control.Biomolecules · 2024Review
- Sterol-Sensing Domain (SSD)-Containing Proteins in Sterol AuxotrophicMicrobiology spectrum · 2023Article
- Saprolegniosis in Amphibians: An Integrated Overview of a Fluffy Killer Disease.Journal of fungi (Basel, Switzerland) · 2022Review
- Article
- Functional Analysis of the C-5 Sterol Desaturase PcErg3 in the Sterol Auxotrophic Oomycete PathogenFrontiers in microbiology · 2022Article
- A Review ofPlants (Basel, Switzerland) · 2021Review
- The mysterious route of sterols in oomycetes.PLoS pathogens · 2021Review
- An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease.Pathogens (Basel, Switzerland) · 2021Article
- The Mevalonate Pathway Is Important for Growth, Spore Production, and the Virulence ofFrontiers in microbiology · 2021Article
- Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens.Journal of fungi (Basel, Switzerland) · 2020Review
- Isolation, molecular identification, and pathological lesions ofVeterinary world · 2020Article
- Identification of Growth Inhibitors of the Fish PathogenFrontiers in microbiology · 2020Article
- Isolation and identification of compounds from the resinous exudate ofBMC chemistry · 2019Article
- Synthesis and Biological Activity of Sterol 14α-Demethylase and Sterol C24-Methyltransferase Inhibitors.Molecules (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A candidate CYP51 gene encoding sterol 14α-demethylase from the fish oomycete pathogen Saprolegnia parasitica (SpCYP51) was identified based on conserved CYP51 residues among CYPs in the genome. It was heterologously expressed in Escherichia coli, purified, and characterized. Lanosterol, eburicol, and obtusifoliol bound to purified SpCYP51 with similar binding affinities (Ks, 3 to 5 μM). Eight pharmaceutical and six agricultural azole antifungal agents bound tightly to SpCYP51, with posaconazole displaying the highest apparent affinity (Kd, ≤3 nM) and prothioconazole-desthio the lowest (Kd, ∼51 nM). The efficaciousness of azole antifungals as SpCYP51 inhibitors was confirmed by 50% inhibitory concentrations (IC50s) of 0.17 to 2.27 μM using CYP51 reconstitution assays. However, most azole antifungal agents were less effective at inhibiting S. parasitica, Saprolegnia diclina, and Saprolegnia ferax growth. Epoxiconazole, fluconazole, itraconazole, and posaconazole failed to inhibit Saprolegnia growth (MIC100, >256 μg ml(-1)). The remaining azoles inhibited Saprolegnia growth only at elevated concentrations (MIC100 [the lowest antifungal concentration at which growth remained completely inhibited after 72 h at 20°C], 16 to 64 μg ml(-1)) with the exception of clotrimazole, which was as potent as malachite green (MIC100, ∼1 μg ml(-1)). Sterol profiles of azole-treated Saprolegnia species confirmed that endogenous CYP51 enzymes were being inhibited with the accumulation of lanosterol in the sterol fraction. The effectiveness of clotrimazole against SpCYP51 activity (IC50, ∼1 μM) and the concentration inhibiting the growth of Saprolegnia species in vitro (MIC100, ∼1 to 2 μg ml(-1)) suggest that clotrimazole could be used against Saprolegnia infections, including as a preventative measure by pretreatment of fish eggs, and for freshwater-farmed fish as well as in leisure activities.
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