{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:11:36Z","timestamp":1779340296190,"version":"3.51.4"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"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. Med."],"abstract":"\n Background<\/jats:title>\n \n Candida albicans<\/jats:italic>\n biofilm formation and azole antifungal resistance are major obstacles to clinical treatment of candidiasis.\n STP1<\/jats:italic>\n and\n MRR2<\/jats:italic>\n are implicated in\n C. albicans<\/jats:italic>\n virulence and stress responses, while\n SAP2<\/jats:italic>\n plays critical roles in biofilm formation and drug resistance. However, the regulatory mechanisms of\n STP1<\/jats:italic>\n and\n MRR2<\/jats:italic>\n on\n SAP2<\/jats:italic>\n expression, biofilm formation, and itraconazole (ITR) resistance, particularly via autophagy, remain unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We compared biofilm-forming ability (via crystal violet assay and microscopy), ITR susceptibility, and autophagic responses among standard ATCC11006,\n STP1<\/jats:italic>\n \u2206\/\u2206,\n MRR2<\/jats:italic>\n \u2206\/\u2206, ITR-sensitive, and ITR-resistant strains. Gene expression levels of\n SAP2<\/jats:italic>\n , and key autophagy-related genes were quantified using RT-qPCR under planktonic and biofilm conditions. The role of autophagy was further investigated using the inducer rapamycin and nitrogen starvation assays.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n ITR-resistant strains exhibited significantly stronger biofilm-forming ability than sensitive strains.\n STP1<\/jats:italic>\n deletion enhanced biofilm formation, while\n MRR2<\/jats:italic>\n deletion impaired it.\n SAP2<\/jats:italic>\n ,\n STP1<\/jats:italic>\n , and\n MRR2<\/jats:italic>\n expression was significantly higher in resistant strains than in sensitive strains under both planktonic and biofilm states, with a significant positive correlation between\n SAP2<\/jats:italic>\n and\n MRR2<\/jats:italic>\n under planktonic conditions (\n r<\/jats:italic>\n \u202f=\u202f0.659,\n p<\/jats:italic>\n \u202f=\u202f0.002). Notably, expression of all tested autophagy-related genes was significantly upregulated in biofilms and in ITR-resistant strains, but was markedly downregulated in both\n STP1\u0394\/\u0394<\/jats:italic>\n and\n MRR2\u0394\/\u0394<\/jats:italic>\n strains. Rapamycin induced autophagosome formation and upregulated\n SAP2<\/jats:italic>\n and\n ATG<\/jats:italic>\n gene expression, but this response was blunted in the knockout strains. Furthermore, both\n STP1\u0394\/\u0394<\/jats:italic>\n and\n MRR2\u0394\/\u0394<\/jats:italic>\n strains displayed increased sensitivity to nitrogen starvation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our findings demonstrate that\n STP1<\/jats:italic>\n and\n MRR2<\/jats:italic>\n are critical regulators of biofilm formation and ITR resistance in\n Candida albicans<\/jats:italic>\n . They exert these effects, at least in part, by modulating the expression of\n SAP2<\/jats:italic>\n and, importantly, by governing the autophagic pathway.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmed.2026.1817039","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:47:52Z","timestamp":1779338872000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The roles of SAP2, STP1, and MRR2 on biofilm formation and itraconazole resistance through autophagy in Candida albicans"],"prefix":"10.3389","volume":"13","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Dermatovenereology, The Second Hospital, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenli","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, The Second Hospital, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, The Second Hospital, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiyao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, The Second Hospital, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, The Second Hospital, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, The Second Hospital, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqin","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, The Second Hospital, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"fuaf013","DOI":"10.1093\/femsre\/fuaf013","article-title":"Vaginal Candida albicans infections: host-pathogen-microbiome interactions","volume":"49","author":"Valentine","year":"2025","journal-title":"FEMS Microbiol Rev"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e0288022","DOI":"10.1128\/mbio.02880-22","article-title":"A clinical study provides the first direct evidence that Interindividual variations in fecal \u03b2-lactamase activity affect the gut 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