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The <jats:italic>Bcr\/CflA<\/jats:italic> efflux system has previously been identified as important for development of <jats:italic>P. mirabilis<\/jats:italic> crystalline biofilms, highlighting the potential for efflux pump inhibitors (EPIs) to control catheter blockage. Here we evaluate the potential for drugs already used in human medicine (fluoxetine and thioridazine) to act as EPIs in <jats:italic>P. mirabilis<\/jats:italic>, and control crystalline biofilm formation. Both fluoxetine and thioridazine inhibited efflux in <jats:italic>P. mirabilis<\/jats:italic>, and molecular modelling predicted both drugs interact strongly with the biofilm-associated <jats:italic>Bcr\/CflA<\/jats:italic> efflux system. Both EPIs were also found to significantly reduce the rate of <jats:italic>P. mirabilis<\/jats:italic> crystalline biofilm formation on catheters, and increase the time taken for catheters to block. Swimming and swarming motilies in <jats:italic>P. mirabilis<\/jats:italic> were also significantly reduced by both EPIs. The impact of these drugs on catheter biofilm formation by other uropathogens (<jats:italic>Escherichia coli<\/jats:italic>, <jats:italic>Pseudomonas aeruginosa<\/jats:italic>) was also explored, and thioridazine was shown to also inhibit biofilm formation in these species. Therefore, repurposing of existing drugs with EPI activity could be a promising approach to control catheter blockage, or biofilm formation on other medical devices.<\/jats:p>","DOI":"10.1038\/s41598-017-12445-w","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T15:26:23Z","timestamp":1505748383000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis"],"prefix":"10.1038","volume":"7","author":[{"given":"Jonathan","family":"Nzakizwanayo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Scavone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirin","family":"Jamshidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Hawthorne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Pelling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Dedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Salvage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte K.","family":"Hind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8526-9169","authenticated-orcid":false,"given":"Fergus M.","family":"Guppy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara M.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-3850","authenticated-orcid":false,"given":"Bhavik A.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-8648","authenticated-orcid":false,"given":"Khondaker M.","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Sutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-9186","authenticated-orcid":false,"given":"Brian V.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,22]]},"reference":[{"key":"12445_CR1","unstructured":"Mobley, H. 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