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Manogepix is a novel antifungal agent that exerts antifungal activity by inhibiting glycosylphosphatidylinositol anchor biosynthesis. Although the mechanisms of resistance of\n                      <jats:italic>Candida<\/jats:italic>\n                      species to manogepix have been reported previously, those of\n                      <jats:italic>C. auris<\/jats:italic>\n                      are yet to be studied. To investigate the resistance mechanisms of\n                      <jats:italic>C. auris<\/jats:italic>\n                      , we exposed a clinical isolate (clade I) to manogepix\n                      <jats:italic>in vitro<\/jats:italic>\n                      and generated strains with reduced susceptibility to manogepix. A search for gain-of-function mutations that upregulate efflux pump expression confirmed the presence of the D865N amino acid mutation in\n                      <jats:italic>TAC1b<\/jats:italic>\n                      . We used the clustered regularly interspaced short palindromic repeats-Cas9 system to create a recovery strain (N865D) in which only this single nucleotide mutation was returned to the wild-type sequence. We generated a mutant strain by introducing only the D865N mutation into the parent strain and a different clade strain (clade III). The D865N mutant strains were clearly less susceptible to manogepix than the parental strains and exhibited high\n                      <jats:italic>CDR1<\/jats:italic>\n                      expression. Moreover, we generated a strain deficient in\n                      <jats:italic>CDR1<\/jats:italic>\n                      and confirmed that this strain had significantly increased susceptibility to manogepix. Thus, the present study demonstrated that the\n                      <jats:italic>TAC1b<\/jats:italic>\n                      mutation in\n                      <jats:italic>C. auris<\/jats:italic>\n                      upregulates\n                      <jats:italic>CDR1<\/jats:italic>\n                      expression and decreases its susceptibility to manogepix.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01508-24","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T09:00:24Z","timestamp":1734512424000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["<i>TAC1b<\/i>\n                    mutation in\n                    <i>Candida auris<\/i>\n                    decreases manogepix susceptibility owing to increased\n                    <i>CDR1<\/i>\n                    expression"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8554-3482","authenticated-orcid":true,"given":"Tatsuro","family":"Hirayama","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences","place":["Nagasaki, Japan"]},{"name":"Department of Respiratory Medicine, Nagasaki University Hospital","place":["Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiga","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki","place":["Miyazaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical 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