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Updated: Sep 21, 2025
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Post-transcriptional control of antifungal resistance in human fungal pathogens
Cheshta Sharma1, David Kadosh1
1Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Abstract:
Global estimates suggest that over 300 million individuals of all ages are affected by serious fungal infections every year, culminating in about 1.7 million deaths. The societal and economic burden on the public health sector due to opportunistic fungal pathogens is quite significant, especially among immunocompromised patients. Despite the high clinical significance of these infectious agents, treatment options are limited with only three major classes of antifungal drugs approved for use. Clinical management of fungal diseases is further compromised by the emergence of antifungal resistant strains. Transcriptional and genetic mechanisms that control drug resistance in human fungal pathogens are well-studied and include drug target alteration, upregulation of drug efflux pumps as well as changes in drug affinity and abundance of target proteins. In this review, we highlight several recently discovered novel post-transcriptional mechanisms that control antifungal resistance, which involve regulation at the translational, post-translational, epigenetic, and mRNA stability levels. The discovery of many of these novel mechanisms has opened new avenues for the development of more effective antifungal treatment strategies and new insights, perspectives, and future directions that will facilitate this process are discussed.
Insights
Antifungal drug resistance in fungi is a growing threat, leading to millions of deaths annually. This review explores novel post-transcriptional mechanisms that regulate resistance, offering new targets for antifungal drug development.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Biology
Background:
- Serious fungal infections affect over 300 million people globally each year, causing 1.7 million deaths.
- Limited antifungal treatment options and emerging drug resistance pose significant public health challenges, particularly for immunocompromised individuals.
- Existing knowledge of antifungal resistance mechanisms primarily focuses on transcriptional and genetic factors.
Approach:
- This review synthesizes recent findings on novel post-transcriptional regulatory mechanisms controlling antifungal resistance.
- It examines regulation at translational, post-translational, epigenetic, and mRNA stability levels.
- The review discusses the implications of these discoveries for developing new antifungal therapies.
Key Points:
- Antifungal resistance is increasingly driven by post-transcriptional modifications beyond genetic changes.
- Mechanisms include translational control, protein modifications, epigenetic alterations, and mRNA stability.
- Understanding these pathways is crucial for overcoming drug resistance in fungal pathogens.
Conclusions:
- Novel post-transcriptional mechanisms offer promising new avenues for developing effective antifungal treatments.
- Further research into these regulatory layers can provide critical insights into fungal drug resistance.
- Targeting these mechanisms could lead to strategies to combat resistant fungal infections.
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