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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\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      strain SC5314, but recent investigations have revealed candidalysin \u201cvariants\u201d of differing amino acid sequence in isolates of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      , and the related species\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">C tropicalis<\/jats:italic>\n                      , suggesting that sequence variation among candidalysins may be widespread in natural populations of these\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      species. Here, we analyzed\n                      <jats:italic toggle=\"yes\">ECE1<\/jats:italic>\n                      gene sequences from 182\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">albicans<\/jats:italic>\n                      isolates, 10\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">dubliniensis<\/jats:italic>\n                      isolates, and 78\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">tropicalis<\/jats:italic>\n                      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\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Fungal infections are a significant burden to health. Candidalysin is a toxin produced by\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">C. tropicalis<\/jats:italic>\n                      , thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin \u201cvariant\u201d toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">C. tropicalis<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03351-23","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T06:19:01Z","timestamp":1719901141000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Variations in candidalysin amino acid sequence influence toxicity and host responses"],"prefix":"10.1128","volume":"15","author":[{"given":"Don N.","family":"Wickramasinghe","sequence":"first","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M.","family":"Lyon","sequence":"additional","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8617-3436","authenticated-orcid":true,"given":"Sejeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia W.","family":"Hepworth","sequence":"additional","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Priest","sequence":"additional","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Maufrais","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INRAe USC 2019, Unit\u00e9 Biologie et Pathog\u00e9nicit\u00e9 Fongiques","place":["Paris, France"]},{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Bioinformatics and Biostatistics Hub","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Ryan","sequence":"additional","affiliation":[{"name":"School of Biomedical and Biomolecular Science and UCD Conway Institute of Biomolecular and Biomedical Research, Conway Institute, University College Dublin","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Permal","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INRAe USC 2019, Unit\u00e9 Biologie et Pathog\u00e9nicit\u00e9 Fongiques","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Oral Biosciences, Dublin Dental University Hospital, and School of Dental Science, Trinity College Dublin","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda A.","family":"McManus","sequence":"additional","affiliation":[{"name":"Division of Oral Biosciences, Dublin Dental University Hospital, and School of Dental Science, Trinity College Dublin","place":["Dublin, 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