Understanding Resistance to Antifungal Drugs in Aspergillus fumigatus
Author Information
Author(s): Hosseini Parham, Keniya Mikhail V., Sagatova Alia A., Toepfer Stephanie, Müller Christoph, Tyndall Joel D. A., Klinger Anette, Fleischer Edmond, Monk Brian C., Calderone Richard
Primary Institution: Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
Hypothesis
The study investigates the molecular basis of intrinsic and acquired resistance to azole antifungals in Aspergillus fumigatus.
Conclusion
The research identifies that the AfCYP51A enzyme is primarily responsible for the intrinsic resistance to fluconazole in Aspergillus fumigatus.
Supporting Evidence
- Aspergillus fumigatus is intrinsically resistant to fluconazole and can acquire resistance to voriconazole.
- The study identified specific mutations in the AfCYP51A enzyme that confer resistance to multiple azole drugs.
- Functional expression of AfCYP51A and AfCYP51B was confirmed in a yeast model system.
Takeaway
This study helps us understand why some fungi are resistant to common antifungal medications, which can help in developing better treatments.
Methodology
The study used crystal structures, molecular models, and expression in Saccharomyces cerevisiae to analyze the resistance mechanisms.
Digital Object Identifier (DOI)
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