{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T15:04:42Z","timestamp":1779548682403,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,20]]},"group-title":"Molecular Biology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The biological conservation between fungi and mammals due to a common ancestor has made development of selective antifungal drugs a difficult challenge. Further complicating this situation is the selection of antifungal drug-resistant organisms during drug treatment. The pathogenic yeast\n                  <jats:italic>Nakaseomyces glabratus<\/jats:italic>\n                  (called here\n                  <jats:italic>Candida glabrata<\/jats:italic>\n                  ) presents an especially challenging organism due to its tendency to frequently lose susceptibility to the major antifungal drug class the azoles. Additionally,\n                  <jats:italic>C. glabrata<\/jats:italic>\n                  develops resistance to echinocandin drugs, a second, more recently described antifungal agent at 10 times the rate of other organisms. Previous work has established that the sterol responsive transcriptional regulator Upc2A is a key determinant of azole susceptibility in\n                  <jats:italic>C. glabrata<\/jats:italic>\n                  and plays a role in echinocandin resistance. We used a biochemical approach to identify proteins that co-purified with Upc2A and identified the Ypk2 AGC kinase as an interacting protein. Strains lacking\n                  <jats:italic>YPK2<\/jats:italic>\n                  exhibited increased susceptibility to fluconazole and the echinocandin caspofungin. A\n                  <jats:italic>ypk2\u0394<\/jats:italic>\n                  strain failed to normally induce transcription of several\n                  <jats:italic>ERG<\/jats:italic>\n                  genes but exhibited normal induction of the\n                  <jats:italic>CDR1<\/jats:italic>\n                  ATP-binding cassette transporter gene. Isogenic\n                  <jats:italic>ypk2\u0394<\/jats:italic>\n                  strains were also highly susceptible to the three major classes of antifungal drugs, indicating that this kinase behaves as a multidrug susceptibility factor. RNA-seq analyses indicated that the transcriptional response to exposure is different for each drug and each response is differentially altered upon loss of Ypk2. Our data indicate that Ypk2 plays an important role in coordinating gene expression that impacts susceptibility to all major antifungal drug classes.\n                <\/jats:p>","DOI":"10.64898\/2026.05.15.725557","type":"posted-content","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:13:49Z","timestamp":1779300829000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Candida glabrata YPK2<\/i>\n                  is a multidrug susceptibility locus"],"prefix":"10.64898","author":[{"given":"Lucia","family":"Simonicova","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Carver College of Medicine University of Iowa Iowa City, IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Conway","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Carver College of Medicine University of Iowa Iowa City, IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute Jena Department of Molecular and Applied Microbiology Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-4193","authenticated-orcid":false,"given":"Axel A.","family":"Brakhage","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute Jena Department of Molecular and Applied Microbiology Jena, Germany"},{"name":"Institute of Microbiology Friedrich Schiller University Jena Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-1120","authenticated-orcid":false,"given":"W. 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