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Fluconazole versus Candida albicans: a complex relationship

J R Graybill1, E Montalbo, W R Kirkpatrick

  • 1Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284, USA. GRAYBILL@UTHSCSA.EDU

Antimicrobial Agents and Chemotherapy
|October 31, 1998
PubMed
Summary
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Candida albicans developing fluconazole resistance shows varied virulence changes. Some resistant strains become less virulent, impacting infection severity, while others maintain virulence, requiring higher drug doses.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance
  • Infectious Diseases

Background:

  • Increasing fluconazole resistance in Candida albicans poses a significant clinical challenge.
  • Understanding the relationship between antifungal resistance and pathogen virulence is crucial for effective treatment strategies.

Purpose of the Study:

  • To investigate the virulence of serial Candida albicans isolates with progressively increasing fluconazole Minimum Inhibitory Concentrations (MICs).
  • To correlate changes in virulence with the development of fluconazole resistance in a murine model of systemic candidiasis.

Main Methods:

  • A murine model was used to assess virulence of serial Candida albicans isolates from patients with oropharyngeal candidiasis.
  • Isolates with increasing fluconazole MICs (susceptible to resistant) were evaluated for their impact on mortality and fungal burden.

Related Experiment Videos

  • Gene expression, specifically for CDR and MDR efflux pumps, was analyzed in relation to virulence and resistance.

    • Main Results:

    • Serial isolates from three of five patients exhibited decreased virulence correlating with increased fluconazole resistance.
    • Reduced virulence was associated with a decreased burden of renal infection in mice.
    • Some resistant isolates showed overexpression of CDR (ABC drug efflux pump), while others overexpressed MDR without significant virulence change.
    • Low-dose fluconazole was ineffective against resistant strains, and high doses were needed for strains with maintained virulence.

    Conclusions:

    • Decreased virulence is associated with increasing fluconazole resistance in some Candida albicans isolates, but not universally.
    • Low-virulence, fluconazole-resistant strains may not consistently cause severe infection.
    • The study highlights the complex interplay between antifungal resistance mechanisms and pathogen fitness.