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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Elucidating drug resistance in human fungal pathogens
Jinglin Lucy Xie1, Elizabeth J Polvi, Tanvi Shekhar-Guturja
1Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Abstract:
Fungal pathogens cause life-threatening infections in immunocompetent and immunocompromised individuals. Millions of people die each year due to fungal infections, comparable to the mortality attributable to tuberculosis or malaria. The three most prevalent fungal pathogens are Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Fungi are eukaryotes like their human host, making it challenging to identify fungal-specific therapeutics. There is a limited repertoire of antifungals in clinical use, and drug resistance and host toxicity compromise the clinical utility. The three classes of antifungals for treatment of invasive infections are the polyenes, azoles and echinocandins. Understanding mechanisms of resistance to these antifungals has been accelerated by global and targeted approaches, which have revealed that antifungal drug resistance is a complex phenomenon involving multiple mechanisms. Development of novel strategies to block the emergence of drug resistance and render resistant pathogens responsive to antifungals will be critical to treating life-threatening fungal infections.
Insights
Millions die annually from fungal infections, necessitating new antifungal drugs. Understanding antifungal resistance mechanisms is key to developing effective treatments for life-threatening fungal diseases.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Drug Discovery
Background:
- Fungal pathogens cause millions of deaths yearly, comparable to tuberculosis or malaria.
- Common culprits include Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.
- Developing targeted antifungal therapies is challenging due to the eukaryotic nature of fungi.
Purpose of the Study:
- To highlight the critical need for novel antifungal strategies.
- To underscore the complexity of antifungal drug resistance.
- To emphasize the importance of understanding resistance mechanisms for effective treatment.
Main Methods:
- Review of current antifungal drug classes (polyenes, azoles, echinocandins).
- Analysis of global and targeted approaches to study antifungal resistance.
- Examination of the multifaceted mechanisms underlying drug resistance.
Main Results:
- Antifungal drug resistance is a complex, multifactorial phenomenon.
- Existing antifungal drug classes face challenges with resistance and host toxicity.
- Limited therapeutic options are currently available for invasive fungal infections.
Conclusions:
- Novel strategies are urgently required to combat emerging antifungal resistance.
- Overcoming resistance is crucial for improving outcomes in life-threatening fungal infections.
- Further research into resistance mechanisms will guide the development of more effective antifungals.
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