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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,2,11]]},"abstract":"<jats:p>\n                    Carbon dioxide is a signaling cue critical for fungal pathogenesis. Ptc2, a type 2C protein phosphatase (PP2C), serves as a conserved CO\n                    <jats:sub>2<\/jats:sub>\n                    sensor in fungi. By combining phosphoproteomic and biochemical assays, we identified Hsp90 as a direct target of Ptc2 at host CO\n                    <jats:sub>2<\/jats:sub>\n                    concentrations and Ssb1 as a Ptc2 target protein regardless of CO\n                    <jats:sub>2<\/jats:sub>\n                    levels in\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , the most prevalent human fungal pathogen. Ptc2 forms reversible condensates at elevated CO\n                    <jats:sub>2<\/jats:sub>\n                    , which enables the recruitment of Hsp90, but not Ssb1, to condensates, allowing efficient dephosphorylation. This process confers an enhanced susceptibility to caspofungin in vitro and during in vivo infection therapy. Importantly, we demonstrate this phenomenon in non-albicans\n                    <jats:italic>Candida<\/jats:italic>\n                    species. Sequential passages of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    in mice with caspofungin treatment readily induce in vivo drug tolerance, causing therapeutic failure. These evolved strains display increased resistance to caspofungin under host concentrations of CO\n                    <jats:sub>2<\/jats:sub>\n                    but remain susceptible in air. Collectively, our study reveals a profound impact of host concentrations of CO\n                    <jats:sub>2<\/jats:sub>\n                    on antifungal drug susceptibility and connects this phenotype to therapeutic outcomes and highlights condensate formation as an efficient means that enables selective recruitment of substrates for certain signaling events.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2417721122","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T11:53:27Z","timestamp":1738756407000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["CO\n                    <sub>2<\/sub>\n                    potentiates echinocandin efficacy during invasive candidiasis therapy via dephosphorylation of Hsp90 by Ptc2 in condensates"],"prefix":"10.1073","volume":"122","author":[{"given":"Mao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, China"]},{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University","place":["Hefei, China"]},{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youzhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Cui","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Xiong","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Yang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Duan","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, China"]},{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianjuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Dermatology Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Su","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University","place":["Wuhan, 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Zhang Y. Lu Data from \u201cGlobal phosphoproteomics identifies potential targets of Ptc2 under host concentrations of carbon dioxide.\u201d ProteomeXchange. https:\/\/proteomecentral.proteomexchange.org\/cgi\/GetDataset?ID=PXD058265. Deposited 26 November 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2417721122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T11:54:21Z","timestamp":1738756461000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2417721122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,2,11]]}},"alternative-id":["10.1073\/pnas.2417721122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2417721122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"assertion":[{"value":"2024-08-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2417721122"}}