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Azole resistance in Aspergillus fumigatus- comprehensive review

Mthokozisi Dladla1, Marieka Gyzenhout2, Gert Marias3

  • 1Department of Genetics, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, 9301, South Africa.

Archives of Microbiology
|June 15, 2024
PubMed

Insights

Azole resistance in Aspergillus fumigatus is a growing concern, leading to treatment failures. Understanding resistance mechanisms, like Cyp51A mutations and efflux pumps, is crucial for combating fungal infections.

Area of Science:

  • Mycology
  • Antimicrobial Resistance
  • Medical Mycology

Background:

  • Aspergillus fumigatus is a common fungus causing respiratory infections, especially in immunocompromised individuals.
  • Azole antifungals are standard treatments, but resistance is emerging.
  • Azole resistance in A. fumigatus is linked to higher treatment failure and mortality.

Purpose of the Study:

  • To provide a comprehensive review of azole antifungal resistance in A. fumigatus.
  • To discuss the mechanisms of azole resistance.
  • To explore the impact of environmental fungicide use on resistant strain spread.

Main Methods:

  • Literature review of studies on azole resistance in A. fumigatus.
  • Analysis of genetic and molecular mechanisms of resistance.
  • Examination of epidemiological data and environmental factors.

Main Results:

  • Azole resistance in A. fumigatus is mediated by acquired (e.g., Cyp51A mutations) and intrinsic mechanisms.
  • Mutations in lanosterol 14-α-demethylase (Cyp51A) reduce azole drug affinity.
  • Efflux pumps contribute to drug resistance by expelling antifungals.
  • Environmental azole fungicide use may drive the selection and spread of resistant strains.

Conclusions:

  • Azole resistance in A. fumigatus poses a significant threat to public health.
  • Understanding resistance mechanisms is key to developing effective treatment and control strategies.
  • Addressing environmental fungicide use is important to mitigate the spread of resistant strains.
Keywords:
Aspergillus fumigatusAspergillosisAzoleDrug resistanceErgosterolInfection

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