A plain language summary of how some fungi samples that show resistance to antifungal medicines have changes in their

Mariana Castanheira1, Timothy D Collingsworth1, Andrew P Davis1

  • 1JMI Laboratories, North Liberty, Iowa, United States of America.

Future Microbiology
|November 3, 2023
PubMed
Abstract

Insights

Fungal infections caused by Aspergillus fumigatus are becoming resistant to azole medicines. Gene mutations are responsible for this resistance, impacting treatment effectiveness for patients.

Area of Science:

  • Medical Mycology
  • Antifungal Resistance
  • Molecular Biology

Background:

  • Aspergillus fumigatus (A. fumigatus) is a fungus causing serious infections.
  • Azole antifungal drugs (isavuconazole, itraconazole, posaconazole, voriconazole) are used to treat these infections.
  • Fungal resistance to azoles is a growing concern, driven by genetic mutations.

Purpose of the Study:

  • To investigate genetic mutations associated with azole resistance in Aspergillus fumigatus.
  • To identify specific genes and mutations conferring resistance to azole antifungals.

Main Methods:

  • Analysis of previously collected clinical samples from A. fumigatus infections.
  • Screening 36 azole-resistant samples for mutations in 50 key genes.
  • Sequencing targeted genes to identify specific resistance mechanisms.

Main Results:

  • 50% (18/36) of samples showed resistance to isavuconazole.
  • Mutations in survival genes (erg3C, erg2, erg7B, erg4B) were found in 12 isavuconazole-resistant samples.
  • The common cyp51A TR34/L98H mutation was identified in 9 samples, with 8 showing resistance to all tested azoles.

Conclusions:

  • Genetic mutations, particularly in cyp51A, are significant drivers of azole resistance in A. fumigatus.
  • Understanding these mutations is crucial for effective antifungal treatment strategies.
  • Continued surveillance of antifungal resistance mechanisms is essential for public health.

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