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Heteroresistance of Cryptococcus gattii to fluconazole

A Varma1, K J Kwon-Chung

  • 1Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.

Antimicrobial Agents and Chemotherapy
|April 14, 2010
PubMed

Insights

All Cryptococcus gattii strains exhibit fluconazole heteroresistance, an intrinsic trait linked to increased virulence. This antifungal resistance mechanism is present even in strains not previously exposed to azoles.

Area of Science:

  • Mycology
  • Antimicrobial Resistance
  • Infectious Diseases

Background:

  • Cryptococcus gattii is an emerging fungal pathogen causing cryptococcosis.
  • Azole antifungals are key treatments, but resistance can develop.
  • Heteroresistance, a form of drug tolerance, is a known mechanism in Cryptococcus neoformans.

Purpose of the Study:

  • To determine the level of fluconazole heteroresistance (LHF) in Cryptococcus gattii strains.
  • To investigate the correlation between LHF, xenobiotic resistance, and virulence.
  • To ascertain if LHF is an intrinsic characteristic of C. gattii.

Main Methods:

  • Analysis of 71 clinical and environmental C. gattii strains.
  • Determination of fluconazole heteroresistance levels (LHF).
  • Assessment of xenobiotic resistance and virulence in relation to LHF.

Main Results:

  • All C. gattii strains showed heteroresistance to fluconazole, with LHFs ranging from 4 to 32 microg/ml.
  • 86% of C. gattii strains had LHFs >=16 microg/ml, compared to 46% of C. neoformans.
  • Higher LHF correlated with increased xenobiotic resistance and significantly higher virulence.
  • Heteroresistance reverted to baseline upon drug-free cultivation.

Conclusions:

  • Fluconazole heteroresistance is an intrinsic trait in C. gattii, similar to C. neoformans.
  • This intrinsic heteroresistance is associated with increased fungal virulence.
  • Understanding LHF is crucial for managing C. gattii infections and antifungal therapy.

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