Related Experiment Video
Updated: May 19, 2026
Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
Identification and analysis of cation channel homologues in human pathogenic fungi
David L Prole1, Colin W Taylor
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom. dp350@cam.ac.uk
Abstract:
Fungi are major causes of human, animal and plant disease. Human fungal infections can be fatal, but there are limited options for therapy, and resistance to commonly used anti-fungal drugs is widespread. The genomes of many fungi have recently been sequenced, allowing identification of proteins that may become targets for novel therapies. We examined the genomes of human fungal pathogens for genes encoding homologues of cation channels, which are prominent drug targets. Many of the fungal genomes examined contain genes encoding homologues of potassium (K(+)), calcium (Ca(2+)) and transient receptor potential (Trp) channels, but not sodium (Na(+)) channels or ligand-gated channels. Some fungal genomes contain multiple genes encoding homologues of K(+) and Trp channel subunits, and genes encoding novel homologues of voltage-gated K(v) channel subunits are found in Cryptococcus spp. Only a single gene encoding a homologue of a plasma membrane Ca(2+) channel was identified in the genome of each pathogenic fungus examined. These homologues are similar to the Cch1 Ca(2+) channel of Saccharomyces cerevisiae. The genomes of Aspergillus spp. and Cryptococcus spp., but not those of S. cerevisiae or the other pathogenic fungi examined, also encode homologues of the mitochondrial Ca(2+) uniporter (MCU). In contrast to humans, which express many K(+), Ca(2+) and Trp channels, the genomes of pathogenic fungi encode only very small numbers of K(+), Ca(2+) and Trp channel homologues. Furthermore, the sequences of fungal K(+), Ca(2+), Trp and MCU channels differ from those of human channels in regions that suggest differences in regulation and susceptibility to drugs.
Insights
Pathogenic fungi possess limited cation channels, unlike humans. These fungal channels differ in sequence, offering potential targets for new antifungal drugs to combat widespread drug resistance.
Area of Science:
- Mycology
- Molecular Biology
- Drug Discovery
Background:
- Fungal infections pose significant health risks, with limited therapeutic options and increasing antifungal drug resistance.
- Genomic sequencing of fungal pathogens enables the identification of novel drug targets.
- Cation channels are established targets for therapeutic intervention.
Purpose of the Study:
- To investigate the presence and characteristics of cation channel homologues in human fungal pathogens.
- To identify potential novel drug targets for antifungal therapies by comparing fungal and human channel proteins.
Main Methods:
- Comparative genomic analysis of human fungal pathogens.
- Identification and characterization of genes encoding potassium (K(+)), calcium (Ca(2+)), and transient receptor potential (Trp) channel homologues.
- Sequence comparison of fungal channels with their human counterparts.
Main Results:
- Fungal genomes encode homologues of K(+), Ca(2+), and Trp channels, but lack sodium (Na(+)) and ligand-gated channels.
- Specific fungal pathogens like *Aspergillus* spp. and *Cryptococcus* spp. possess mitochondrial calcium uniporter (MCU) homologues.
- Pathogenic fungi exhibit a significantly reduced repertoire of K(+), Ca(2+), and Trp channels compared to humans.
- Fungal channel sequences display distinct regions compared to human channels, suggesting differential regulation and drug susceptibility.
Conclusions:
- Pathogenic fungi possess a limited and distinct set of cation channels compared to humans.
- These identified fungal cation channel homologues represent promising targets for the development of novel antifungal drugs.
- Differences in channel structure may explain differential drug responses and guide the design of targeted therapies.
More Related Videos
Related Concept Videos
01:28Fungal Phylum Microsporidia
01:15Antifungal Agents