{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:08:14Z","timestamp":1793120894845,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0108679"],"award-info":[{"award-number":["JP25fk0108679"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP26fk0108758"],"award-info":[{"award-number":["JP26fk0108758"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K18807"],"award-info":[{"award-number":["25K18807"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Morinomiyako Medical Research Foundation","award":["2025-01-043"],"award-info":[{"award-number":["2025-01-043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Candida auris (Candidozyma auris) is an emerging multidrug-resistant fungal pathogen that poses a significant global health threat. However, the molecular mechanisms underlying its virulence remain incompletely understood. In this study, we performed in vivo transcriptome analysis using an immunosuppressed mouse gastrointestinal infection model to identify genes associated with host adaptation and virulence during infection. By comparing fungal transcriptomes obtained from colonization and dissemination sites with those from\u00a0in vitro cultures, we identified genes that were consistently upregulated during infection. Among these genes, the unfolded protein response regulator HAC1 was selected as a candidate virulence-associated gene for further analysis. Reverse transcription PCR and sequencing analyses revealed that\u00a0HAC1 mRNA in C. auris undergoes an unconventional splicing event of 287 bp that is enhanced under endoplasmic reticulum stress conditions. The excised region spans the annotated open reading frame boundary, suggesting that the translated region of\u00a0HAC1 may require re-evaluation. Notably, a proportion of HAC1 transcripts appeared to be spliced even under non-stress conditions, indicating a detectable basal level of the unfolded protein response. Differences in splicing dynamics were also observed among clade strains. Functional analyses demonstrated that deletion of\u00a0HAC1 increased sensitivity to endoplasmic reticulum stress. The HAC1 deletion mutant also exhibited reduced virulence in both Galleria mellonella and immunosuppressed mouse infection models, as evidenced by delayed host mortality and decreased fungal burdens, respectively. These findings indicate that HAC1 contributes to endoplasmic reticulum stress adaptation and survival in the host environment and identify\u00a0HAC1 as a virulence-associated gene in C. auris.<\/jats:p>","DOI":"10.1093\/mmy\/myag067","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T12:36:11Z","timestamp":1782736571000},"source":"Crossref","is-referenced-by-count":1,"title":["<i>HAC1<\/i>\n                    contributes to stress adaptation and virulence in the emerging fungal pathogen\n                    <i>Candida auris<\/i>"],"prefix":"10.1093","volume":"64","author":[{"given":"Sayoko","family":"Oiki","sequence":"first","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security. Toyama 1-23-1 Department of Fungal Infection, , Shinjuku-ku, Tokyo 162-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-716X","authenticated-orcid":false,"given":"Masahiro","family":"Abe","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security. Toyama 1-23-1 Department of Fungal Infection, , Shinjuku-ku, Tokyo 162-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Hirasawa","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security. Toyama 1-23-1 Department of Fungal Infection, , Shinjuku-ku, Tokyo 162-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Koizumi","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security. Toyama 1-23-1 Department of Fungal Infection, , Shinjuku-ku, Tokyo 162-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amato","family":"Otani","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security. Toyama 1-23-1 Department of Fungal Infection, , Shinjuku-ku, Tokyo 162-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Shinohara","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security. Toyama 1-23-1 Department of Fungal Infection, , Shinjuku-ku, Tokyo 162-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8942-0869","authenticated-orcid":false,"given":"Yoshitsugu","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security. 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