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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
08:45

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

Published on: December 28, 2017

Molecular and biochemical mechanisms of drug resistance in fungi

H Yamaguchi1

  • 1Teikyo University Institute of Medical Mycology, 259 Otsuka, Hachioji-shi, Tokyo 192-395, Japan.

Nihon Ishinkin Gakkai Zasshi = Japanese Journal of Medical Mycology
|October 28, 1999
PubMed

Insights

Antifungal drug resistance is a growing concern. This review details molecular mechanisms of resistance to amphotericin B, flucytosine, and azoles, highlighting challenges in treating fungal infections.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance
  • Molecular Biology

Background:

  • Systemic fungal infections pose significant health risks.
  • Emerging resistance to key antifungal agents necessitates understanding molecular mechanisms.
  • Amphotericin B (AMPH), flucytosine (5-FC), and azoles are crucial for treating invasive fungal diseases.

Purpose of the Study:

  • To review current knowledge on resistance mechanisms of AMPH, 5-FC, and azoles (particularly fluconazole) in fungi.
  • To elucidate resistance at molecular and cellular levels.
  • To identify key challenges in antifungal therapy due to resistance.

Main Methods:

  • Literature review of published studies on antifungal resistance.
  • Analysis of molecular and cellular mechanisms of drug resistance.
  • Biochemical characterization of resistant fungal strains.

Main Results:

  • Limited resistance reported for AMPH and 5-FC, with described mechanisms including decreased ergosterol and UMP-pyrophosphorylase lesions.
  • Increasing resistance to azoles, especially fluconazole (FLCZ), in Candida species.
  • Azole resistance mechanisms involve altered sterol biosynthesis, target modification, and efflux pumps, with reduced drug access to P450 14 DM being clinically significant.

Conclusions:

  • Understanding fungal resistance mechanisms is critical for effective antifungal drug development and treatment strategies.
  • Efflux pumps and target overproduction are key factors in azole resistance.
  • Further research is needed to identify all mechanisms contributing to azole resistance.

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