{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:44:19Z","timestamp":1792637059126,"version":"4.5.0"},"reference-count":252,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T00:00:00Z","timestamp":1700352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Northern Ontario Academic Medicine Association (NOAMA) AFP Innovation Fund","award":["A-22-14"],"award-info":[{"award-number":["A-22-14"]}]},{"name":"Northern Ontario Academic Medicine Association (NOAMA) AFP Innovation Fund","award":["7400852"],"award-info":[{"award-number":["7400852"]}]},{"name":"Northern Ontario Academic Medicine Association (NOAMA) AFP Innovation Fund","award":["RGPIN-2022-03159"],"award-info":[{"award-number":["RGPIN-2022-03159"]}]},{"name":"Northern Ontario School of Medicine University (NOSM U) Faculty Association Research Development Award","award":["A-22-14"],"award-info":[{"award-number":["A-22-14"]}]},{"name":"Northern Ontario School of Medicine University (NOSM U) Faculty Association Research Development Award","award":["7400852"],"award-info":[{"award-number":["7400852"]}]},{"name":"Northern Ontario School of Medicine University (NOSM U) Faculty Association Research Development Award","award":["RGPIN-2022-03159"],"award-info":[{"award-number":["RGPIN-2022-03159"]}]},{"name":"Northern Ontario Heritage Fund Corporation (NOHFC) Internship Fund","award":["A-22-14"],"award-info":[{"award-number":["A-22-14"]}]},{"name":"Northern Ontario Heritage Fund Corporation (NOHFC) Internship Fund","award":["7400852"],"award-info":[{"award-number":["7400852"]}]},{"name":"Northern Ontario Heritage Fund Corporation (NOHFC) Internship Fund","award":["RGPIN-2022-03159"],"award-info":[{"award-number":["RGPIN-2022-03159"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant","award":["A-22-14"],"award-info":[{"award-number":["A-22-14"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant","award":["7400852"],"award-info":[{"award-number":["7400852"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant","award":["RGPIN-2022-03159"],"award-info":[{"award-number":["RGPIN-2022-03159"]}]},{"name":"Northern Cancer Foundation","award":["A-22-14"],"award-info":[{"award-number":["A-22-14"]}]},{"name":"Northern Cancer Foundation","award":["7400852"],"award-info":[{"award-number":["7400852"]}]},{"name":"Northern Cancer Foundation","award":["RGPIN-2022-03159"],"award-info":[{"award-number":["RGPIN-2022-03159"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis\/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance.<\/jats:p>","DOI":"10.3390\/cells12222655","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:30:50Z","timestamp":1700440250000},"page":"2655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":188,"title":["Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Candida Species"],"prefix":"10.3390","volume":"12","author":[{"given":"Karolina M.","family":"Czajka","sequence":"first","affiliation":[{"name":"Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada"},{"name":"School of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5925-306X","authenticated-orcid":false,"given":"Danielle","family":"Brabant-Kirwan","sequence":"additional","affiliation":[{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey A.","family":"Santi","sequence":"additional","affiliation":[{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Verschoor","sequence":"additional","affiliation":[{"name":"Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada"},{"name":"School of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada"},{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasu D.","family":"Appanna","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Singh","sequence":"additional","affiliation":[{"name":"Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada"},{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah P.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada"},{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujeenthar","family":"Tharmalingam","sequence":"additional","affiliation":[{"name":"Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada"},{"name":"School of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada"},{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bhattacharya, S., Sae-Tia, S., and Fries, B.C. 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