{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:10:15Z","timestamp":1790475015925,"version":"4.1.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K22AI110541"],"award-info":[{"award-number":["K22AI110541"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI127942"],"award-info":[{"award-number":["R21AI127942"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI141829"],"award-info":[{"award-number":["R21AI141829"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01A134796"],"award-info":[{"award-number":["R01A134796"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM120642"],"award-info":[{"award-number":["R01GM120642"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE022550"],"award-info":[{"award-number":["R01DE022550"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["214229_Z_18Z"],"award-info":[{"award-number":["214229_Z_18Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UTHSC College of Pharmacy Center for Pediatric and Experimental Therapeutics"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from a polypeptide (Ece1p) encoded by the\n                    <jats:italic>ECE1<\/jats:italic>\n                    gene, plays a crucial role in driving immunopathology at the vaginal mucosa. This study aimed to determine if expression and\/or processing of Ece1p differs across\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    isolates and whether this partly underlies differential pathogenicity observed clinically. Using a targeted sequencing approach, we determined that isolate 529L harbors a similarly expressed, yet distinct Ece1p isoform variant that encodes for a predicted functional candidalysin; this isoform was conserved amongst a collection of clinical isolates. Expression of the\n                    <jats:italic>ECE1<\/jats:italic>\n                    open reading frame (ORF) from 529L in an SC5314-derived\n                    <jats:italic>ece1<\/jats:italic>\n                    \u0394\/\u0394 strain resulted in significantly reduced vaginopathogenicity as compared to an isogenic control expressing a wild-type (WT)\n                    <jats:italic>ECE1<\/jats:italic>\n                    allele. However,\n                    <jats:italic>in vitro<\/jats:italic>\n                    challenge of vaginal epithelial cells with synthetic candidalysin demonstrated similar toxigenic activity amongst SC5314 and 529L isoforms. Creation of an isogenic panel of chimeric strains harboring swapped Ece1p peptides or HiBiT tags revealed reduced secretion with the ORF from 529L that was associated with reduced virulence. A genetic survey of 78 clinical isolates demonstrated a conserved pattern between Ece1p P2 and P3 sequences, suggesting that substrate specificity around Kex2p-mediated KR cleavage sites involved in protein processing may contribute to differential pathogenicity amongst clinical isolates. Therefore, we present a new mechanism for attenuation of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    virulence at the\n                    <jats:italic>ECE1<\/jats:italic>\n                    locus.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009884","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T13:41:07Z","timestamp":1631281267000},"page":"e1009884","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":75,"title":["A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis"],"prefix":"10.1371","volume":"17","author":[{"given":"Junyan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubertine M. E.","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Sansevere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Allert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3824-6829","authenticated-orcid":true,"given":"Katherine S.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0401-6790","authenticated-orcid":true,"given":"David J.","family":"Lowes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0227-653X","authenticated-orcid":true,"given":"Andrew C.","family":"Dixson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2865-2441","authenticated-orcid":true,"given":"Zhenbo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9733-9152","authenticated-orcid":true,"given":"Christian","family":"DeJarnette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Tournu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen E.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco N.","family":"Barrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6028-0425","authenticated-orcid":true,"given":"Bernhard","family":"Hube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-7917","authenticated-orcid":true,"given":"Julian R.","family":"Naglik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-2077","authenticated-orcid":true,"given":"Brian M.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ppat.1009884.ref001","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1128\/CMR.00076-09","article-title":"Candida infections of the genitourinary tract","volume":"23","author":"J Achkar","year":"2010","journal-title":"Clin Microbiol Rev"},{"key":"ppat.1009884.ref002","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1056\/NEJM199712253372607","article-title":"Vaginitis","volume":"337","author":"J Sobel","year":"1997","journal-title":"N Engl J Med"},{"key":"ppat.1009884.ref003","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1128\/IAI.72.5.2939-2946.2004","article-title":"An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis","volume":"72","author":"P 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