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Variations in candidalysin amino acid sequence influence toxicity and host responses
Don N Wickramasinghe1, Claire M Lyon1, Sejeong Lee1
1Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom.
Mbio
|July 2, 2024
Summary
Candida infections cause significant health issues. This study identifies new variants of the candidalysin toxin in Candida species, revealing differences in their ability to damage host cells and influence infection severity.
Area of Science:
- Medical Mycology
- Molecular Biology
- Host-Pathogen Interactions
Background:
- Millions of mucosal infections are caused by *Candida albicans* annually.
- Candidalysin, a peptide toxin, destabilizes host cell membranes, contributing to disease and immunopathology.
- Previous research identified candidalysins in *C. albicans*, *C. dubliniensis*, and *C. tropicalis*.
Purpose of the Study:
- To identify and characterize candidalysin variants in *C. albicans*, *C. dubliniensis*, and *C. tropicalis*.
- To assess the biological activity and biophysical properties of identified candidalysin variants.
Main Methods:
- Analysis of *ECE1* gene sequences from 182 *C. albicans*, 10 *C. dubliniensis*, and 78 *C. tropicalis* isolates.
- Application of candidalysin variants to epithelial cells to evaluate cellular damage, metabolic activity, and signaling pathways.
- Biophysical analyses to determine variant interactions with lipid bilayers and membrane permeabilization.
Main Results:
- Ten candidalysin variants were identified in *C. albicans*, 3 in *C. dubliniensis*, and 2 in *C. tropicalis*.
- Candidalysin variants exhibited differential effects on epithelial cells, including variations in damage, calcium influx, MAPK signaling, and cytokine secretion.
- Biophysical studies showed distinct abilities of variants to interact with and permeabilize membranes.
Conclusions:
- Intraspecies variation in candidalysin amino acid sequence is widespread in medically relevant *Candida* species.
- Identified candidalysin variants possess differing biological activities, influencing pathogenicity.
- Understanding candidalysin variation is crucial for comprehending *Candida* pathogenesis and developing targeted therapies.
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