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Emergence of Azole Resistance in Aspergillus

Nathan P Wiederhold1, Thomas F Patterson2

  • 1Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Seminars in Respiratory and Critical Care Medicine
|September 24, 2015
PubMed

Insights

Azole antifungal resistance in Aspergillus species, particularly Aspergillus fumigatus, is increasing due to CYP51A gene mutations. This resistance poses a significant threat, with limited treatment options and high mortality rates for invasive infections.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance
  • Molecular Biology

Background:

  • Growing concern over azole antifungal resistance in Aspergillus species, impacting treatment efficacy.
  • Acquired resistance documented in Aspergillus fumigatus, affecting both exposed patients and azole-naive individuals.
  • Clinical and environmental emergence of azole-resistant Aspergillus strains worldwide.

Purpose of the Study:

  • To summarize the mechanisms and implications of azole resistance in Aspergillus species.
  • To highlight the clinical challenges and treatment limitations for infections caused by resistant strains.
  • To underscore the environmental dissemination of resistance mechanisms.

Main Methods:

  • Review of clinical and environmental data on azole resistance in Aspergillus.
  • Analysis of genetic mutations in the CYP51A gene associated with resistance.
  • Examination of resistance mechanisms including point mutations and promoter region alterations.

Main Results:

  • Key resistance mechanisms involve point mutations in CYP51A (e.g., TR34/L98H, TR46/Y121F/T289A) and promoter tandem repeats.
  • These mutations confer resistance to itraconazole, voriconazole, and posaconazole.
  • Environmental detection of resistance mechanisms raises concerns about agricultural fungicide impact and spread.

Conclusions:

  • Azole resistance in Aspergillus fumigatus is a significant clinical problem with limited therapeutic alternatives.
  • High mortality rates are associated with invasive infections caused by azole-resistant A. fumigatus.
  • Environmental spread of resistance necessitates further investigation and monitoring.

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