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Despite numerous studies, the molecular-pathophysiology during VVC and its commensal state within the host remains elusive. To address this, we performed a comprehensive computational analysis by integrating RNA-Seq datasets from both host and pathogen. Differentially expressed genes were identified and used to construct three network models: within the pathogen, host, and host-pathogen interaction. Subsequent inter-network nodes mapping enabled us to attain two distinct condition-specific fungal targeted networks in the host, during VVC (466 nodes and 496 edges) and commensal state (162 nodes and 176 edges), which were validated by condition-specific immune response by gene ontology analysis. Intending to target pathogenesis while preserving its commensal integrity, we identified an exclusive fungal protein Zfu2p that acts as a master regulator in the gene regulatory network of the pathogen. It promotes pathogenic attributes through its target gene\n                    <jats:italic>RNR22<\/jats:italic>\n                    and interacts with the host protein UBC. Subsequently, the drug repurposing strategy coupled with molecular dynamics analysis identified Ergotamine as a promising candidate, which may disrupt biofilm formation while preserving commensal balance. This study offers insights into VVC pathophysiology and suggests a targeted therapy, though experimental validation of Ergotamine\u2019s efficacy remains essential.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-46848-5","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:36:05Z","timestamp":1778675765000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Devising a Zfu2p targeted antifungal strategy that may preserve commensalism while suppressing Candida albicans virulence during vulvovaginal candidiasis"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2371-8301","authenticated-orcid":false,"given":"Ali Rejwan","family":"Kabir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anis Ahmad","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6699-4074","authenticated-orcid":false,"given":"Joydeep","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-508X","authenticated-orcid":false,"given":"Soumita","family":"Podder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"46848_CR1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s40588-023-00190-w","volume":"10","author":"ID Jacobsen","year":"2023","unstructured":"Jacobsen, I. 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