{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:04:56Z","timestamp":1785175496225,"version":"3.55.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Deanship of Research and Graduate Studies at King Khalid University","award":["RGP1\/8\/47"],"award-info":[{"award-number":["RGP1\/8\/47"]}]},{"name":"the Deanship of Research and Graduate Studies at King Khalid University","award":["RGP1\/8\/47"],"award-info":[{"award-number":["RGP1\/8\/47"]}]},{"name":"the Deanship of Research and Graduate Studies at King Khalid University","award":["RGP1\/8\/47"],"award-info":[{"award-number":["RGP1\/8\/47"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Proteus mirabilis is a major uropathogen implicated in catheter-associated urinary tract infections and infection-induced urolithiasis, often exhibiting multidrug resistance. Improving the solubility and bioactivity of existing drugs represents a promising pharmaceutical strategy to overcome these challenges. In this study, inclusion complexes of metronidazole with \u03b1-cyclodextrin (\u03b1-CD), \u03b2-cyclodextrin (\u03b2-CD), and hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) were prepared using physical mixing and kneading methods. Complexes were characterized using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). In vitro release behaviour,\u00a0minimum inhibitory concentration (MIC), and effects at sub-MIC levels on motility, urease-associated phenotype, and biofilm formation were evaluated. \u03b2-CD and HP-\u03b2-CD systems demonstrated improved release profiles compared to metronidazole alone. While MIC values remained within the mg\/mL range, HP-\u03b2-CD complexes showed reduced MIC relative to aqueous metronidazole, achieving a four-fold reduction in MIC. At sub-MIC concentrations, \u03b2-CD and HP-\u03b2-CD formulations were associated with significant suppression of motility, reduced urease-associated phenotypes, and inhibition of biofilm formation. Molecular docking suggested spatial compatibility between metronidazole and cyclodextrins, though mechanistic conclusions remain predictive. These findings indicate that cyclodextrin-based complexation enhances physicochemical performance of metronidazole and may support adjunctive anti-virulence modulation in P. mirabilis. Further mechanistic and in-vivo studies are required to validate translational relevance.<\/jats:p>","DOI":"10.1371\/journal.pone.0353058","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:39:46Z","timestamp":1785173986000},"page":"e0353058","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cyclodextrin inclusion complexes enhance the solubility and anti-virulence activity of metronidazole against uropathogenic Proteus mirabilis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6094-5653","authenticated-orcid":true,"given":"Rehab Mahmoud","family":"Abd El-Baky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Fathalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala 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