{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:25:03Z","timestamp":1783524303034,"version":"3.55.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K15438, 23K06533"],"award-info":[{"award-number":["21K15438, 23K06533"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment.\n                      <jats:italic>Trichophyton rubrum<\/jats:italic>\n                      is the most commonly isolated fungus in dermatophytosis. In\n                      <jats:italic>T. rubrum<\/jats:italic>\n                      , we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast\n                      <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                      polyamine transport kinase 2 (Ptk2), and found that\n                      <jats:italic>T. rubrum<\/jats:italic>\n                      Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both\n                      <jats:italic>T. rubrum<\/jats:italic>\n                      and\n                      <jats:italic>S. cerevisiae<\/jats:italic>\n                      , Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in\n                      <jats:italic>S. cerevisiae<\/jats:italic>\n                      . Overexpression of\n                      <jats:italic>T. rubrum<\/jats:italic>\n                      Pma1 (TrPma1) in\n                      <jats:italic>T. rubrum<\/jats:italic>\n                      Ptk2 knockout strain (\u0394TrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01609-23","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T09:01:52Z","timestamp":1712134912000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["The Ptk2-Pma1 pathway enhances tolerance to terbinafine in\n                    <i>Trichophyton rubrum<\/i>"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-3147","authenticated-orcid":true,"given":"Masaki","family":"Ishii","sequence":"first","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino 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