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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond
Yunjin Lee1, Emily Puumala1, Nicole Robbins1
1Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, Ontario M5G 1M1, Canada.
Abstract:
Fungal infections are a major contributor to infectious disease-related deaths across the globe. Candida species are among the most common causes of invasive mycotic disease, with Candida albicans reigning as the leading cause of invasive candidiasis. Given that fungi are eukaryotes like their human host, the number of unique molecular targets that can be exploited for antifungal development remains limited. Currently, there are only three major classes of drugs approved for the treatment of invasive mycoses, and the efficacy of these agents is compromised by the development of drug resistance in pathogen populations. Notably, the emergence of additional drug-resistant species, such as Candida auris and Candida glabrata, further threatens the limited armamentarium of antifungals available to treat these serious infections. Here, we describe our current arsenal of antifungals and elaborate on the resistance mechanisms Candida species possess that render them recalcitrant to therapeutic intervention. Finally, we highlight some of the most promising therapeutic strategies that may help combat antifungal resistance, including combination therapy, targeting fungal-virulence traits, and modulating host immunity. Overall, a thorough understanding of the mechanistic principles governing antifungal drug resistance is fundamental for the development of novel therapeutics to combat current and emerging fungal threats.
Insights
Fungal infections cause many global deaths, with Candida species posing a significant threat due to drug resistance. New antifungal strategies are crucial to combat these evolving pathogens.
Area of Science:
- Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Fungal infections, particularly invasive candidiasis, are a leading cause of mortality worldwide.
- Limited unique molecular targets and emerging drug resistance in Candida species, including Candida albicans, Candida auris, and Candida glabrata, challenge current antifungal therapies.
- Existing antifungal drug classes are insufficient to combat the growing threat of resistant fungal infections.
Purpose of the Study:
- To review the current landscape of antifungal drugs.
- To elucidate the resistance mechanisms employed by Candida species.
- To explore promising therapeutic strategies against antifungal resistance.
Main Methods:
- Review of existing literature on antifungal drugs and resistance mechanisms in Candida species.
- Analysis of current and emerging therapeutic approaches.
- Discussion of novel strategies including combination therapy, targeting virulence factors, and host immune modulation.
Main Results:
- The limited number of antifungal drug classes and the rapid development of resistance in Candida populations significantly compromise treatment efficacy.
- Candida species possess diverse resistance mechanisms, rendering them difficult to treat with existing therapies.
- Emerging drug-resistant species like Candida auris and Candida glabrata exacerbate the clinical challenge.
Conclusions:
- A comprehensive understanding of antifungal resistance mechanisms is essential for developing novel therapeutics.
- Promising strategies to combat antifungal resistance include combination therapy, targeting fungal virulence, and host-directed immune therapies.
- Continued research is vital to address the global threat of invasive fungal infections and antifungal resistance.
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