ArticlePLoS neglected tropical diseases2025
Itraconazole resistance in Madurella fahalii linked to a distinct homolog of the gene encoding cytochrome P450 14-α sterol demethylase (CYP51).
Article in PLoS neglected tropical diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A qPCR identification scheme to differentiate actinomycetoma from eumycetoma.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Simultaneous Detection of Four Madurella Species Using Loop-Mediated Isothermal Amplification (LAMP) for Eumycetoma Diagnosis.Mycopathologia · 2025Article
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5 authors.
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Abstract
backgroundMycetoma is a deep fungal infection caused by several microorganisms, with Madurella mycetomatis being the most common causative agent. Another related species, Madurella fahalii, is also known to cause eumycetoma. However, unlike M. mycetomatis, M. fahalii exhibits resistance to itraconazole, the standard treatment for eumycetoma, and the underlying cause of this resistance remains unknown. Therefore, understanding the mechanism of this resistance is critical for developing more effective therapies. PRINCIPAL
findingsUsing the high-quality draft genome sequence of Madurella fahalii IFM 68171, we identified two copies of the gene encoding cytochrome P450 14-α sterol demethylase (CYP51), the target enzyme of itraconazole. These include a gene conserved among Madurella species (Mfcyp51A1) and a M. fahalii-specific gene (Mfcyp51A2). Both genes are actively transcribed in M. fahalii and are upregulated in response to itraconazole. Furthermore, heterologous expression in Saccharomyces cerevisiae revealed that transformants carrying the Mfcyp51A2 gene exhibited reduced susceptibility to itraconazole compared to those with Mfcyp51A1.
conclusionWe demonstrated that itraconazole resistance in M. fahalii may be attributed to the presence of an additional CYP51 gene. This study represents the first report on the physiological characteristics of Madurella species using genetic engineering techniques.
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