Principal Investigator: Dr Brian Vaughan Jones

Lead institution: University of Brighton

Award amount: £71,914

 

Evaluating the potential for efflux inhibitors to control infection, encrustation and blockage of urinary catheters

This grant was awarded to Dr Brian Jones in 2014 to investigate strategies for preventing the infection and subsequent blockage of catheters by the bacterial species, Proteus mirabilis. The research team’s previous work had shown that specialised components of the P. mirabilis cell, which act like “pumps” and is referred to as efflux systems (EPIs), were important to the ability of P. mirabilis to infect and block catheters. The team consequently planned to test if drugs that block these pumps could be used to prevent P. mirabilis infections and the blockage of catheters by this organism.

Dr Jones and his team successfully tested the potential for existing drugs to function as EPIs in P. mirabilis and demonstrated the ability of selected EPIs to inhibit crystalline biofilm formation and extend catheter lifespan. Specifically they found that the EPIs, fluoxetine and thioridazine, inhibited efflux in P. mirabilis. 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. The impact of these drugs on catheter biofilm formation by other uropathogens (Escherichia coliPseudomonas aeruginosa) was also explored, and thioridazine was shown to also inhibit biofilm formation in these species. Therefore, the repurposing of existing drugs with EPI activity could be a promising approach to control catheter blockage, or biofilm formation on other medical devices.

Following the conclusion of this grant in 2017, the paper “Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis’ was published in Scientific Reports. We are thrilled to learn that the paper received 525 article views in 2017, placing it as one of the top 100 read microbiology papers for Scientific Reports in 2017 (out of the more than 2000 it published). In fact, it was in the top 25.

Co-applicants on the grant were: Dr Bhavik Anil Patel and Dr Lara-Marie Barnes

Dr Jones is now a Reader in Molecular and Medical Microbiology at the University of Bath.