Triazole Resistance in Aspergillus Species: An Emerging Problem

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Rocio Garcia-Rubio1, Manuel Cuenca-Estrella1, Emilia Mellado2

  • 1Mycology Department, Centro Nacional de Microbiologia, Instituto de Salud Carlos III (ISCIII), Carretera Majadahonda-Pozuelo Km2, Majadahonda, 28220, Madrid, Spain.

Drugs
|February 26, 2017
PubMed

Insights

Azole resistance in Aspergillus fumigatus, a major cause of invasive aspergillosis, is increasing due to clinical and agricultural azole use. Understanding resistance mechanisms is crucial for effective treatment and prevention.

Area of Science:

  • Medical Mycology
  • Antifungal Resistance
  • Fungal Pathogenesis

Background:

  • Aspergillus fumigatus is a prevalent fungus causing invasive aspergillosis in immunocompromised individuals.
  • Azole antifungals are first-line treatments, but resistance is a growing global concern.
  • Resistance threatens both clinical antifungal therapy and agricultural applications of azoles.

Purpose of the Study:

  • To review the epidemiology of azole resistance in Aspergillus fumigatus.
  • To elucidate the predominant molecular mechanisms driving azole resistance.
  • To discuss the clinical implications and future research directions for azole resistance.

Main Methods:

  • Literature review of studies on Aspergillus fumigatus azole resistance.
  • Analysis of epidemiological data on resistance prevalence.
  • Examination of molecular mechanisms including cyp51A gene mutations and promoter alterations.

Main Results:

  • Azole resistance in A. fumigatus arises from both medical (treatment-driven) and environmental (agricultural use-driven) routes.
  • Key resistance mechanisms involve alterations in the cyp51A gene, encoding the azole target 14-α sterol demethylase.
  • Tandem repeat insertions in the promoter and point mutations within the cyp51A gene are predominant.

Conclusions:

  • Azole resistance in A. fumigatus poses a significant threat to public health and agriculture.
  • Understanding the distinct evolutionary pathways of resistance is vital for intervention strategies.
  • Further research is needed to combat the rising challenge of azole-resistant Aspergillus fumigatus infections.

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