Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis

Jonathan Nzakizwanayo, Paola Scavone, Shirin Jamshidi, Joseph A. Hawthorne, Harriet Pelling, Cinzia Dedi, Jonathan P. Salvage, Charlotte Hind, Fergus M. Guppy, Lara M. Barnes, Bhavik A. Patel, Khondaker M. Rahman, Mark J. Sutton, Brian V. Jones*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Proteus mirabilis forms extensive crystalline biofilms on indwelling urethral catheters that block urine flow and lead to serious clinical complications. The Bcr/CflA efflux system has previously been identified as important for development of P. mirabilis 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 P. mirabilis, and control crystalline biofilm formation. Both fluoxetine and thioridazine inhibited efflux in P. mirabilis, and molecular modelling predicted both drugs interact strongly with the biofilm-associated Bcr/CflA efflux system. Both EPIs were also found to significantly reduce the rate of P. mirabilis crystalline biofilm formation on catheters, and increase the time taken for catheters to block. Swimming and swarming motilies in P. mirabilis were also significantly reduced by both EPIs. The impact of these drugs on catheter biofilm formation by other uropathogens (Escherichia coli, Pseudomonas aeruginosa) 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.

Original languageEnglish
Article number12222
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2017

Bibliographical note

Funding Information:
This study was primarily supported by the Dunhill Medical Trust (DMT), proving funding to J.N., P.S., B.A.P., L.M.B. and B.V.J. under grant number R394/1114. H.P., B.V.J., M.J.S., and J.N. are also supported by the Medical Research Council (Grants MR/P015956/1 and MR/N006496/1). Molecular docking simulations were supported by the King’s College London High Performance Computing Facility (Kings HPC3, Ada Cluster).

Publisher Copyright:
© 2017 The Author(s).


Dive into the research topics of 'Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis'. Together they form a unique fingerprint.

Cite this