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To overcome the resistance, research on antifungal agent sensitizers has attracted considerable attention. Omeprazole and lansoprazole were found to inhibit the growth of sensitive <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> and hyphae formation in a high dose, respectively. This study aimed to determine the interactions of common clinically proton pump inhibitors (PPIs) and fluconazole both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> and to further explore the possible mechanisms. <jats:italic>In vitro<\/jats:italic>, the tested PPIs all acted synergistically with fluconazole against both resistant <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> planktonic cells and biofilms preformed for \u226412\u2009h with the minimum inhibitory concentration of fluconazole decreased from &gt;512\u2009\u03bcg\/mL to 1\u20134\u2009\u03bcg\/mL. <jats:italic>In vivo<\/jats:italic>, PPIs plus fluconazole prolonged the survival rate of infected <jats:italic>Galleria mellonella<\/jats:italic> larvae by two-fold compared with that for the fluconazole monotherapy group and significantly reduced the tissue damage of infected larvae. Mechanism studies showed that PPIs significantly suppressed efflux pump activity, which is the common resistance mechanism of <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic>, and significantly inhibited the virulence factors: phospholipase activity and morphology switching. These findings will provide new insights into antifungal agent discovery and potential approaches for the treatment of candidiasis caused by resistant <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/s41598-019-57174-4","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T11:03:28Z","timestamp":1579172608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans"],"prefix":"10.1038","volume":"10","author":[{"given":"Mengjiao","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixiang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"57174_CR1","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1056\/NEJMra1315399","volume":"373","author":"BJ Kullberg","year":"2015","unstructured":"Kullberg, B. 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