Azole resistance in Candida albicans

Area of Science:

• Mycology
• Infectious Diseases
• Pharmacology

Background:

• Chronic mucocutaneous candidosis (CMC) can be challenging to treat.
• Ketoconazole is a commonly used antifungal agent for Candida infections.
• Relapse of CMC suggests potential antifungal resistance.

Purpose of the Study:

• To investigate the antifungal resistance mechanisms in Candida albicans isolates from relapsed CMC patients.
• To determine the cross-resistance patterns of these isolates to other antifungal agents.
• To elucidate the cellular basis of observed drug resistance.

Main Methods:

• In vitro testing of Candida albicans isolates against ketoconazole and ICI 153,066.
• Animal models of vaginal and systemic infection were used to assess treatment efficacy.
• Assays for ergosterol biosynthesis inhibition and amino acid uptake were performed.
• Radiolabeling studies were conducted to track ICI 153,066 uptake.

Main Results:

• Two Candida albicans isolates exhibited abnormal responses to ketoconazole in vitro and in vivo.
• These isolates showed cross-resistance to the triazole antifungal ICI 153,066.
• Resistance was associated with impaired ergosterol biosynthesis inhibition and amino acid uptake.
• Failure to uptake radiolabeled ICI 153,066 indicated cell membrane alterations.

Conclusions:

• The findings are consistent with the development of drug resistance to ketoconazole in these Candida albicans isolates.
• Cell membrane changes, rather than internal enzymology, appear to be the primary mechanism of resistance.
• This highlights the importance of monitoring antifungal resistance in patients with recurrent infections.