{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:19:03Z","timestamp":1788913143090,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Invasive candidiasis (IC) is an increasingly common, expensive, and potentially fatal infection. However, IC caused by multiple <jats:italic>Candida<\/jats:italic> species is rarely reported in China. Herein, we revealed a complex IC caused by multiple <jats:italic>Candida<\/jats:italic> species, comprising the rare <jats:italic>C. norvegensis<\/jats:italic>, <jats:italic>C. albicans<\/jats:italic>, <jats:italic>C. glabrata<\/jats:italic>, and <jats:italic>C. tropicalis<\/jats:italic>. The resistance mechanism of azole and echinocandin resistance were explored further.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The isolates were confirmed using internal transcribed spacer (ITS) sequencing. The resistance mechanisms were investigated using PCR-based sequencing, quantitative real-time reverse transcription PCR, and rhodamine 6G efflux quantification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Antifungal susceptibility testing showed this complex infection was associated with cross-resistance to azole and echinocandin drugs. For <jats:italic>C. glabrata<\/jats:italic>, the acquired echinocandin resistance was likely caused by a novel mutational pattern (1,3-beta-D-glucan synthase subunits FKS1-S629P and FKS2-W1497stop) while the acquired azole resistance in <jats:italic>C. glabrata<\/jats:italic> RJ05 was related to complex mechanisms including enhanced efflux activity, pleiotropic drug resistance 1 (PDR1) mutation, and increased expression of <jats:italic>Candida<\/jats:italic> drug resistance 1 (CDR1) and CDR2. Additionally, the azole resistance of <jats:italic>C. tropicalis<\/jats:italic> was caused by two lanosterol 14-alpha demethylase (ERG11) mutations: Y132F and S154F.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed a case of clinically complex, multiple <jats:italic>Candida<\/jats:italic> invasive infections, further uncovering the resistance mechanisms to azoles and echinocandins. These findings provide valuable references for the diagnosis and treatment of invasive candidiasis (IC) in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1550894","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T23:33:37Z","timestamp":1742945617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Emergence of invasive candidiasis with multiple Candida species exhibiting azole and echinocandin resistance"],"prefix":"10.3389","volume":"16","author":[{"given":"Si-Jia","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Tao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jie","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3389\/fcimb.2013.00074","article-title":"Interactions between copy number and expression level of genes involved in fluconazole resistance in Candida glabrata","volume":"3","author":"Abbes","year":"2013","journal-title":"Front. 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