{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:35:14Z","timestamp":1757576114421,"version":"3.41.2"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Science and Technology Development Plan of Suzhou","award":["SLJ2022018"],"award-info":[{"award-number":["SLJ2022018"]}]},{"name":"Scientific Research Project of Suzhou Commission of Health","award":["GSWS2020028"],"award-info":[{"award-number":["GSWS2020028"]}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81402978"],"award-info":[{"award-number":["81402978"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,12,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Candida albican<\/jats:italic>\n            s is a prevalent opportunistic human fungal pathogen. Echinocandins are first-line drugs for the treatment of invasive candidiasis. Molecular mechanisms of resistance to echinocandins have been extensively studied; however, the effect of physiological factors on antifungal efficacy of echinocandins is unexplored. Here, we found temperature-modulated susceptibility to caspofungin in medium-independent and strain background-independent manner in\n            <jats:italic>C. albicans<\/jats:italic>\n            . Deletions of protein kinase C (PKC) pathway and calcineurin-Crz1 signaling pathway genes conferred hypersensitivity to caspofungin, but only deletion or pharmacological inhibition of calcineurin subunits inverted the temperature effect on susceptibility to caspofungin. Furthermore, the enhanced growth at lower temperature was not due to altered expression of some established genes such as\n            <jats:italic>FKS<\/jats:italic>\n            ,\n            <jats:italic>CHS<\/jats:italic>\n            , or\n            <jats:italic>CHT<\/jats:italic>\n            genes; PKC or calcineurin pathway genes; or\n            <jats:italic>HSP90<\/jats:italic>\n            . The expressions of other heat shock protein genes, including\n            <jats:italic>HSP12<\/jats:italic>\n            and\n            <jats:italic>HSP70<\/jats:italic>\n            , were higher at lower temperature. We posit that the temperature-modulated susceptibility to caspofungin is a non-canonical mechanism that is dependent on heat shock proteins and calcineurin.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Echinocandins are the newest antifungal drugs and are first-line treatment option for life-threatening systemic infections. Due to lack of consensus regarding what temperature should be used when evaluating susceptibility of yeasts to echinocandins, typically either 30\u00b0C, 35\u00b0C, or 37\u00b0C is used. However, the impact of temperature on antifungal efficacy of echinocandins is unexplored. In the current study, we demonstrated that\n              <jats:italic>Candida albicans<\/jats:italic>\n              laboratory strain SC5314 was more susceptible to caspofungin at 37\u00b0C than at 30\u00b0C. We also found that calcineurin was required for temperature-modulated caspofungin susceptibility. Surprisingly, the altered caspofungin susceptibility was not due to differential expression of some canonical genes such as\n              <jats:italic>FKS<\/jats:italic>\n              ,\n              <jats:italic>CHS<\/jats:italic>\n              , or\n              <jats:italic>CHT<\/jats:italic>\n              genes. The molecular mechanism of temperature-modulated caspofungin susceptibility is undetermined and deserves further investigations.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01790-23","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T14:03:08Z","timestamp":1700056988000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Susceptibility to caspofungin is regulated by temperature and is dependent on calcineurin in\n            <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"11","author":[{"given":"Lijun","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Ultrasound Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 960 Hospital of PLA, Jinan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 960 Hospital of PLA, Jinan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2363-0745","authenticated-orcid":false,"given":"Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3272-1363","authenticated-orcid":false,"given":"Yubo","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 960 Hospital of PLA, Jinan, 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