Variations in candidalysin amino acid sequence influence toxicity and host responses Article Swipe
Don N. Wickramasinghe
,
Claire M. Lyon
,
Sejeong Lee
,
Olivia W. Hepworth
,
Emily Priest
,
Corinne Maufrais
,
Adam P. Ryan
,
Emmanuelle Permal
,
Derek J. Sullivan
,
Brenda A. McManus
,
Bernhard Hube
,
Geraldine Butler
,
Christophe d’Enfert
,
Julian R. Naglik
,
Jonathan P. Richardson
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1128/mbio.03351-23
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1128/mbio.03351-23
Candida albicans causes millions of mucosal infections in humans annually. Hyphal overgrowth on mucosal surfaces is frequently associated with tissue damage caused by candidalysin, a secreted peptide toxin that destabilizes the plasma membrane of host cells thereby promoting disease and immunopathology. Candidalysin was first identified in C. albicans strain SC5314, but recent investigations have revealed candidalysin “variants” of differing amino acid sequence in isolates of C. albicans , and the related species C. dubliniensis , and C tropicalis , suggesting that sequence variation among candidalysins may be widespread in natural populations of these Candida species. Here, we analyzed ECE1 gene sequences from 182 C . albicans isolates, 10 C . dubliniensis isolates, and 78 C . tropicalis isolates and identified 10, 3, and 2 candidalysin variants in these species, respectively. Application of candidalysin variants to epithelial cells revealed differences in the ability to cause cellular damage, changes in metabolic activity, calcium influx, MAPK signalling, and cytokine secretion, while biophysical analyses indicated that variants exhibited differences in their ability to interact with and permeabilize a membrane. This study identifies candidalysin variants with differences in biological activity that are present in medically relevant Candida species. IMPORTANCE Fungal infections are a significant burden to health. Candidalysin is a toxin produced by Candida albicans that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species C. dubliniensis and C. tropicalis , thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin “variant” toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of C. albicans , C. dubliniensis , and C. tropicalis and identified candidalysin variants in all three species. When applied to epithelial cells, candidalysin variants differed in their ability to cause damage, activate intracellular signaling pathways, and induce innate immune responses, while biophysical analysis revealed differences in the ability of candidalysin variants to interact with lipid bilayers. These findings suggest that intraspecies variation in candidalysin amino acid sequence may influence fungal pathogenicity.
Related Topics
Concepts
Candida albicans
Biology
Corpus albicans
Candida dubliniensis
Microbiology
Toxin
Peptide sequence
Candida tropicalis
Gene
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1128/mbio.03351-23
- OA Status
- gold
- Cited By
- 6
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4400247750
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4400247750Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1128/mbio.03351-23Digital Object Identifier
- Title
-
Variations in candidalysin amino acid sequence influence toxicity and host responsesWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-07-02Full publication date if available
- Authors
-
Don N. Wickramasinghe, Claire M. Lyon, Sejeong Lee, Olivia W. Hepworth, Emily Priest, Corinne Maufrais, Adam P. Ryan, Emmanuelle Permal, Derek J. Sullivan, Brenda A. McManus, Bernhard Hube, Geraldine Butler, Christophe d’Enfert, Julian R. Naglik, Jonathan P. RichardsonList of authors in order
- Landing page
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https://doi.org/10.1128/mbio.03351-23Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://doi.org/10.1128/mbio.03351-23Direct OA link when available
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Candida albicans, Biology, Corpus albicans, Candida dubliniensis, Microbiology, Toxin, Peptide sequence, Candida tropicalis, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
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6Total citation count in OpenAlex
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2025: 6Per-year citation counts (last 5 years)
- References (count)
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47Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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