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Emerging evidence suggests that intraspecies and interspecies QS plays an important role in antimicrobial resistance in microbial communities. However, the relationship between interkingdom QS and antimicrobial resistance is largely unknown. Here, we demonstrate that interkingdom QS interactions between a bacterium, <jats:italic>Pseudomonas aeruginosa<\/jats:italic> and a yeast, <jats:italic>Candida albicans<\/jats:italic>, induce the resistance of the latter to a widely used antifungal fluconazole. Phenotypic, transcriptomic, and proteomic analyses reveal that <jats:italic>P. aeruginosa\u2019s<\/jats:italic> main QS molecule, N-(3-Oxododecanoyl)-L-homoserine lactone, induces candidal resistance to fluconazole by reversing the antifungal\u2019s effect on the ergosterol biosynthesis pathway. Accessory resistance mechanisms including upregulation of <jats:italic>C. albicans<\/jats:italic> drug-efflux, regulation of oxidative stress response, and maintenance of cell membrane integrity, further confirm this phenomenon. These findings demonstrate that <jats:italic>P. aeruginosa<\/jats:italic> QS molecules may confer protection to neighboring yeasts against azoles, in turn strengthening their co-existence in hostile polymicrobial infection sites.<\/jats:p>","DOI":"10.1038\/s41598-020-64761-3","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T10:03:33Z","timestamp":1588932213000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Fluconazole resistance in Candida albicans is induced by Pseudomonas aeruginosa quorum sensing"],"prefix":"10.1038","volume":"10","author":[{"given":"H. M. H. 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