{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:24:37Z","timestamp":1790223877837,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      is the leading cause of vulvovaginal candidiasis (VVC), yet the extent to which strain-level variation influences pathogenic mechanisms remains unclear. Candidalysin, a peptide toxin encoded by\n                      <jats:italic toggle=\"yes\">ECE1<\/jats:italic>\n                      , is a key driver of epithelial damage and immunopathology, but its role has been largely defined in a limited number of laboratory strains. Here, we analyzed a panel of 27 vaginal clinical isolates obtained from asymptomatic, acute VVC, and recurrent VVC (RVVC) subjects and performed whole-genome sequencing and broad phenotypic profiling, including growth, biofilm formation, stressor and antifungal susceptibility, filamentation, and\n                      <jats:italic toggle=\"yes\">ECE1<\/jats:italic>\n                      expression. To directly assess the role of candidalysin,\n                      <jats:italic toggle=\"yes\">ece1<\/jats:italic>\n                      \u0394\/\u0394 mutant pairs were generated for each isolate and evaluated\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and in a murine model of VVC. Isolates exhibited substantial, context-dependent phenotypic heterogeneity, and pathogenic traits did not cluster according to clinical classification. Despite this diversity, deletion of\n                      <jats:italic toggle=\"yes\">ECE1<\/jats:italic>\n                      universally reduced epithelial damage and inflammatory responses\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and attenuated immunopathological markers\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Notably, the reference strain SC5314 displayed enhanced virulence compared to most clinical isolates, further demonstrating that it represents a hypervirulent outlier. Collectively, these findings demonstrate that the virulence determinant candidalysin operates across a highly heterogeneous population of vaginal clinical isolates, and its expression is positively correlated to pathogenicity. These studies further highlight the importance of delineating virulence attributes beyond the lens of SC5314.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00304-26","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:00:46Z","timestamp":1782129646000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Phenotypic and genotypic analysis of\n                    <i>Candida albicans<\/i>\n                    vaginal isolates reveals that\n                    <i>ECE1<\/i>\n                    expression underpins pathogenicity"],"prefix":"10.1128","volume":"94","author":[{"given":"Amirhossein","family":"Davari","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmaceutical Sciences Graduate Program, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyan","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, USA"]},{"id":[{"id":"https:\/\/ror.org\/000b7ms85","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Light Industry and Food Science, Guangdong Provincial Key Laboratory of Lingnan Specialty Food Science and Technology, Academy of Contemporary Agricultural Engineering Innovations, Zhongkai University of Agriculture and Engineering","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jabez P.","family":"Fortwendel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmaceutical Sciences Graduate Program, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Luna-Tapia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Lowes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Miao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmaceutical Sciences Graduate Program, University of Tennessee Health Science Center","place":["Memphis, USA"]},{"id":[{"id":"https:\/\/ror.org\/05h4zj272","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Harbor-UCLA Medical Center","place":["Torrance, USA"]},{"id":[{"id":"https:\/\/ror.org\/025j2nd68","id-type":"ROR","asserted-by":"publisher"}],"name":"The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center","place":["Torrance, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1910-6558","authenticated-orcid":true,"given":"Hubertine M. E.","family":"Willems","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"DeJarnette","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Peters","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048zq6v82","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Ahmadi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmaceutical Sciences Graduate Program, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surabhi","family":"Naik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01k9xac83","id-type":"ROR","asserted-by":"publisher"}],"name":"Research Bioinformatics Core, Rush University","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5261-6267","authenticated-orcid":true,"given":"Marc","family":"Swidergall","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05h4zj272","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Harbor-UCLA Medical Center","place":["Torrance, USA"]},{"id":[{"id":"https:\/\/ror.org\/025j2nd68","id-type":"ROR","asserted-by":"publisher"}],"name":"The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center","place":["Torrance, USA"]},{"name":"David Geffen School of Medicine at University of California, Los Angeles","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-0679","authenticated-orcid":true,"given":"P. David","family":"Rogers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048zq6v82","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-4609","authenticated-orcid":true,"given":"Jack D.","family":"Sobel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01070mq45","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine, Wayne State University School of Medicine","place":["Detroit, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-3130","authenticated-orcid":true,"given":"Glen E.","family":"Palmer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, USA"]},{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-2077","authenticated-orcid":true,"given":"Brian M.","family":"Peters","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, USA"]},{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011684"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-019-0748-8"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof6010027"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-11-169"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.06.067"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.2939-2946.2004"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00211-17"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00709-25"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01417-13"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00645-17"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010012"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02878-21"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.555363"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-71459-z"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009884"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03351-23"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.039354-0"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioflm.2023.100162"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01117"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-21846-1"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nport.2008.141"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1179\/joc.2007.19.3.283"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpmc.124"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-61701-5"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01777-19"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02630-21"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.07.004"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00469-16"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02669"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00107-23"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026580"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.11.021"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2011.10.006"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.17874"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2021.104893"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.837536"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00157-25"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-025-02923-w"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2016.01.002"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00724-15"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2005.01165.x"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsle.2005.02.015"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","unstructured":"Garrison EP Marth GT. 2012. Haplotype-based variant detection from short-read sequencing. arXiv. doi:10.48550\/arXiv.1207.3907","DOI":"10.48550\/arXiv.1207.3907"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.102"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt476"},{"key":"e_1_3_5_49_2","unstructured":"Ortiz EM. 2019. Vcf2phylip v2.0: convert a VCF matrix into several matrix formats for phylogenetic analysis. https:\/\/doi.org\/10.5281\/zenodo.2540861"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu300"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1177\/11779322211059238"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00062-08"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbx108"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab705"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12493-y"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2014.0157"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163962"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00715-18"},{"key":"e_1_3_5_60_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi: approved standard","author":"Rex JH","year":"2008","unstructured":"Rex JH. 2008. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi: approved standard. Clinical and Laboratory Standards Institute."},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00181-23"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpmc.60"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.08.002"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0809532"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00304-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00304-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:30:23Z","timestamp":1785353423000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00304-26"}},"subtitle":[],"editor":[{"given":"Andreas J.","family":"B\u00e4umler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":64,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,14]]}},"alternative-id":["10.1128\/iai.00304-26"],"URL":"https:\/\/doi.org\/10.1128\/iai.00304-26","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"assertion":[{"value":"2026-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00304-26"}}