ArticleFrontiers in microbiology2016
Δ(24)-Sterol Methyltransferase Plays an Important Role in the Growth and Development of Sporothrix schenckii and Sporothrix brasiliensis.
Article in Frontiers in microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Therapeutic alternatives for sporotrichosis induced by wild-type and non-wild-type Sporothrix schenckii through in vitro and in vivo assessment of enilconazole, isavuconazole, posaconazole, and terbinafine.Scientific reports · 2025Article
- Review
- Zinc(II)-Sterol Hydrazone Complex as a Potent Anti-Pharmaceutics · 2023Article
- Sporotrichosis: A Review of a Neglected Disease in the Last 50 Years in Brazil.Microorganisms · 2022Review
- Current Progress on Epidemiology, Diagnosis, and Treatment of Sporotrichosis and Their Future Trends.Journal of fungi (Basel, Switzerland) · 2022Review
- Unravelling the myth surrounding sterol biosynthesis as plausible target for drug design against leishmaniasis.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021Review
- The Search for Putative Hits in Combating Leishmaniasis: The Contributions of Natural Products Over the Last Decade.Natural products and bioprospecting · 2021Review
- The Role of Macrophages in the Host's Defense againstPathogens (Basel, Switzerland) · 2021Review
- Review
- The threat of emerging and re-emerging pathogenic Sporothrix species.Mycopathologia · 2020Review
- Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans.Fungal genetics and biology : FG & B · 2020Article
- α-Bisabolol inhibits Aspergillus fumigatus Af239 growth via affecting microsomal ∆World journal of microbiology & biotechnology · 2017Article
- Zoonotic Epidemic of Sporotrichosis: Cat to Human Transmission.PLoS pathogens · 2017Review
- Adamantylidene-substituted alkylphosphocholine TCAN26 is more active against Sporothrix schenckii than miltefosine.Memorias do Instituto Oswaldo Cruz · 2016Article
- Sporotrichosis: an update on epidemiology, etiopathogenesis, laboratory and clinical therapeutics.Anais brasileiros de dermatologiaArticle
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of Δ(24)-sterol methyltransferase (24-SMT) in Sporothrix schenckii sensu stricto and Sporothrix brasiliensis was investigated in vitro. The effects on fungal growth and sterol composition of the 24-SMT inhibitor 22-hydrazone-imidazolin-2-yl-chol-5-ene-3β-ol (H3) were compared to those of itraconazole. MIC and MFC analysis showed that H3 was more effective than itraconazole against both species in both their filamentous and yeast forms. H3 showed fungistatic activity in a time-kill assay, with inhibitory activity stronger than that of itraconazole. GC analysis of cell sterol composition showed that sterols present in control cells (ergosterol and precursors) were completely replaced by 14α-methylated sterols after H3 exposure. Itraconazole only partially inhibited ergosterol synthesis but completely arrested synthesis of other sterols found in control cells, promoting accumulation of nine 14α-methyl sterols. Based on these results, we propose a schematic model of sterol biosynthesis pathways in S. schenckii and S. brasiliensis. Effects on cell morphology due to 24-SMT inhibition by H3 as analyzed by SEM and TEM included irregular cell shape, reduced cytoplasmic electron-density, and reduced thickness of the microfibrillar cell wall layer. Moreover, 24-SMT inhibition by H3 promoted mitochondrial disturbance, as demonstrated by alterations in MitoTracker(®) Red CMXRos fluorescence intensity evaluated by flow cytometry. When used in conjunction with itraconazole, H3 enhanced the effectiveness of itraconazole against all tested strains, reducing at least half (or more) the MIC values of itraconazole. In addition, cytotoxicity assays revealed that H3 was more selective toward these fungi than was itraconazole. Thus, 24-SMT inhibition by H3 was an effective antifungal strategy against S. schenckii and S. brasiliensis. Inhibition of the methylation reaction catalyzed by 24-SMT has a strong antiproliferative effect via disruption of ergosterol homeostasis, suggesting that this enzyme is a promising target for novel antifungal therapies against sporotrichosis, either as sole treatments or in combination with itraconazole.
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