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Managing these infections poses a serious challenge to clinicians, especially with the emergence of fluconazole-resistant (FLC-R)\n                      <jats:italic>Candida<\/jats:italic>\n                      species. In this study, we aimed to determine the mechanisms of fluconazole resistance in urinary\n                      <jats:italic>Candida<\/jats:italic>\n                      spp. isolated from hospitalized patients in Alexandria, Egypt, assess the correlation between fluconazole resistance and virulence, and explore potential treatment options for UTIs caused by FLC-R\n                      <jats:italic>Candida<\/jats:italic>\n                      strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fluconazole susceptibility testing of 34 urinary\n                      <jats:italic>Candida<\/jats:italic>\n                      isolates indicated that 76.5% were FLC-R, with a higher prevalence of resistance recorded in non-\n                      <jats:italic>albicans Candida<\/jats:italic>\n                      spp. (88.9%) than in\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      (62.5%). The calculated Spearman\u2019s correlation coefficients implied significant positive correlations between fluconazole minimum inhibitory concentrations and both biofilm formation and phospholipase production. Real-time PCR results revealed that most FLC-R isolates (60%) significantly overexpressed at least one efflux pump gene, while 42.3% significantly upregulated the\n                      <jats:italic>ERG11<\/jats:italic>\n                      gene. The most prevalent mutation detected upon\n                      <jats:italic>ERG11<\/jats:italic>\n                      sequencing was G464S, which is conclusively linked to fluconazole resistance. The five repurposed agents: amikacin, colistin, dexamethasone, ketorolac, and sulfamethoxazole demonstrated variable fluconazole-sensitizing activities in vitro, with amikacin, dexamethasone, and colistin being the most effective. However, the fluconazole\/colistin combination produced a notable reduction (49.1%) in bladder bioburden, a 50% decrease in the inflammatory response, and tripled the median survival span relative to the untreated murine models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The fluconazole\/colistin combination offers a promising treatment option for UTIs caused by FLC-R\n                      <jats:italic>Candida<\/jats:italic>\n                      , providing an alternative to the high-cost, tedious process of novel antifungal drug discovery in the battle against antifungal resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-024-03512-0","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T07:01:42Z","timestamp":1727766102000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6330-5357","authenticated-orcid":false,"given":"Hend","family":"Zeitoun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1231-4646","authenticated-orcid":false,"given":"Rawan A.","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0768-4068","authenticated-orcid":false,"given":"Nadia M.","family":"El-Guink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1860-1402","authenticated-orcid":false,"given":"Nesrin S.","family":"Tolba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9073-5032","authenticated-orcid":false,"given":"Nelly M.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"issue":"7","key":"3512_CR1","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.cmi.2019.03.028","volume":"25","author":"KE Pristov","year":"2019","unstructured":"Pristov KE, Ghannoum MA. 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The urine samples were collected by the routine laboratory facility of Alexandria Main University Hospital, and <i>Candida<\/i> isolates were provided anonymously for use in this study. The authors did not have any contact with the patients. Approval was granted by the Ethics Committee of Alexandria University, Faculty of Medicine, under IRB number: 00012098 and FWA number: 00018699. All animal experimental procedures were carried out according to the international and institutional ethical guidelines and were ethically approved by the Institutional Animal Care and Use Committee (IACUC) of the Faculty of Pharmacy, Alexandria University (IACUC Project # 06\/2021\/10\/17\/1\/110). All animal procedures and experiments reported in this study were performed following the ARRIVE guidelines on animal research and in a manner that ensures minimal animal suffering.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"383"}}