Azole resistance mechanisms in Aspergillus: update and recent advances

Area of Science:

• Medical Mycology
• Infectious Diseases
• Molecular Biology

Background:

• Invasive aspergillosis (IA) is a severe fungal infection primarily caused by Aspergillus fumigatus, affecting immunocompromised individuals.
• Voriconazole is the primary antifungal treatment, but rising azole resistance is leading to treatment failures and increased mortality.
• Other Aspergillus species, including Aspergillus flavus and Aspergillus terreus, can also cause IA.

Purpose of the Study:

• To review and discuss the current molecular data on azole resistance in clinically significant Aspergillus species.
• To elucidate the known mechanisms of azole resistance, focusing on target protein modifications and efflux pump activity.
• To highlight emerging and less characterized resistance mechanisms in Aspergillus.

Main Methods:

• Literature review of published studies on azole resistance in Aspergillus.
• Analysis of molecular mechanisms including mutations in target genes (e.g., Cyp51).
• Investigation of the role of efflux pumps (ATP-binding cassette and major facilitator superfamily) in resistance.

Main Results:

• Identified key molecular mechanisms contributing to azole resistance in Aspergillus species.
• Detailed the involvement of the target enzyme Cyp51 and efflux pumps in conferring resistance.
• Highlighted the need for further research into novel and uncharacterized resistance pathways.

Conclusions:

• Molecular understanding of azole resistance mechanisms is crucial for combating invasive aspergillosis.
• Emerging resistance necessitates continuous monitoring and research into alternative therapeutic strategies.
• This review provides a comprehensive overview of current knowledge on Aspergillus azole resistance.