ArticleScientific reports2017
Intrinsic short-tailed azole resistance in mucormycetes is due to an evolutionary conserved aminoacid substitution of the lanosterol 14α-demethylase.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 87 citations in OpenAlex.
- Molecular Mechanisms, Diagnosis, and Therapeutic Strategies of Antifungal Resistance in Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2026Review
- Genotype-Phenotype Relationships in Azole-ResistantJournal of fungi (Basel, Switzerland) · 2026Review
- Nanoemulsion-Based Tea Tree Oil: A New Frontier in Enhancing Clotrimazole Antifungal Activity.Molecular biotechnology · 2026Article
- Coordinated gene family evolution shapes the genome of dimorphic Mucorales.Nature communications · 2026Article
- The molecular basis of intrinsic resistance to azoles inAntimicrobial agents and chemotherapy · 2026Article
- Understanding the biology of mucormycosis using contemporary omics tools: a review.Biotechnologia · 2026Review
- When Should Clinical Mycology Laboratories Perform Antifungal Susceptibility Testing? Revisiting Practice Through the Lens of Intrinsic Resistance.Mycopathologia · 2025Review
- Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus.The Journal of antimicrobial chemotherapy · 2025Article
- Monoclonal Antibodies Can Aid in the Culture-Based Detection and Differentiation ofAntibodies (Basel, Switzerland) · 2025Article
- Antidermatophytic activity of Curcuma longa against Trichophyton spp.: compound identification and molecular docking to lanosterol 14α-demethylase.BMC complementary medicine and therapies · 2025Article
- Antifungal resistance: Emerging mechanisms and implications (Review).Molecular medicine reports · 2025Review
- The Heterogenous Presentation of Hepatic Mucormycosis in Adults: A Case Report and Review of the Literature.Journal of fungi (Basel, Switzerland) · 2025Article
- Intrinsic resistance to short-tailed azoles in the basal fungusFrontiers in microbiology · 2025Article
- The Molecular Basis of the Intrinsic and Acquired Resistance to Azole Antifungals inJournal of fungi (Basel, Switzerland) · 2024Article
- A Comprehensive Analysis of the Lipidomic Signatures inJournal of fungi (Basel, Switzerland) · 2024Article
- Article
- Harnessing Machine Learning to Uncover Hidden Patterns in Azole-Resistant CYP51/ERG11 Proteins.Microorganisms · 2024Article
- Molecular mechanisms that govern infection and antifungal resistance in Mucorales.Microbiology and molecular biology reviews : MMBR · 2024Review
- Article
- IntegratingCurrent research in microbial sciences · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucormycoses are emerging and potentially lethal infections. An increase of breakthrough infections has been found in cohorts receiving short-tailed azoles prophylaxis (e.g. voriconazole (VCZ)). Although VCZ is ineffective in vitro and in vivo, long-tailed triazoles such as posaconazole remain active against mucormycetes. Our goal was to validate the molecular mechanism of resistance to short-tailed triazoles in Mucorales. The paralogous cytochrome P450 genes (CYP51 F1 and CYP51 F5) of Rhizopus arrhizus, Rhizopus microsporus, and Mucor circinelloides were amplified and sequenced. Alignment of the protein sequences of the R. arrhizus, R. microsporus, and M. circinelloides CYP51 F1 and F5 with additional Mucorales species (n = 3) and other fungi (n = 16) confirmed the sequences to be lanosterol 14α-demethylases (LDMs). Sequence alignment identified a pan-Mucorales conservation of a phenylalanine129 substitution in all CYP51 F5s analyzed. A high resolution X-ray crystal structure of Saccharomyces cerevisiae LDM in complex with VCZ was used for generating a homology model of R. arrhizus CYP51 F5. Structural and functional knowledge of S. cerevisiae CYP51 shows that the F129 residue in Mucorales CYP51 F5 is responsible for intrinsic resistance of Mucorales against short-tailed triazoles, with a V to A substitution in Helix I also potentially playing a role.
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