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Sphingolipids (SLs), known for their interclade heterogeneity, play a crucial role in antifungal resistance. This study examined the SL landscape in two drug-susceptible clade II isolates, C-line and P-line, from distinct geographical origins, which were experimentally evolved to develop stable fluconazole (FLC) resistance. The progenitors displayed distinct SL profiles, P1 had higher PhytoCer and \u03b1OHPhytoCer, indicating a more active acidic SL biosynthesis branch, whereas C1 exhibited elevated \u03b1OHGlcCer, \u03b1OHCer, and LCBs, reflecting a greater role of the neutral biosynthesis branch. The principal component analysis also confirmed distinct segregation of the two progenitors. Upon evolution, P1.1 and C1.1 adaptors showed significant SL alterations. P1.1 exhibited PhytoCer enrichment, while C1.1 showed reduced \u03b1OHGlcCer alongside increased PhytoCer, dhCer, and \u03b1OHPhytoCer levels. Notably, \u03b1OHGlcCer remained unchanged in P1.1, whereas LCBs and \u03b1OHPhytoCer decreased compared to P1. Despite these lineage-specific differences between the progenitors, both evolved replicates exhibited increased PhytoCer as a common denominator like what is also observed in clinical FLC-resistant isolates. These findings highlight intraclade SL variability and suggest that specific SLs contribute to FLC resistance in C. auris.<\/jats:p>","DOI":"10.1093\/femsyr\/foaf030","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T16:27:04Z","timestamp":1748622424000},"source":"Crossref","is-referenced-by-count":0,"title":["The experimentally evolved fluconazole-resistant clade II isolates of <i>Candidozyma auris<\/i> exhibit a distinct lipid compositional landscape, highlighting intraclade sphingolipid heterogeneity"],"prefix":"10.1093","volume":"25","author":[{"given":"Praveen","family":"Kumar","sequence":"first","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University , Gurugram, Haryana, 122413 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8266-8605","authenticated-orcid":false,"given":"Basharat","family":"Ali","sequence":"additional","affiliation":[{"name":"Amity 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