title: Bacteriophage Can Prevent Encrustation and Blockage of Urinary Catheters by Proteus mirabilis.
abstract: Proteus mirabilis forms dense crystalline biofilms on catheter surfaces that occlude urine flow, leading to serious clinical complications in long-term catheterized patients, but there are presently no truly effective approaches to control catheter blockage by this organism. This study evaluated the potential for bacteriophage therapy to control P. mirabilis infection and prevent catheter blockage. Representative in vitro models of the catheterized urinary tract, simulating a complete closed drainage system as used in clinical practice, were employed to evaluate the performance of phage therapy in preventing blockage. Models mimicking either an established infection or early colonization of the catheterized urinary tract were treated with a single dose of a 3-phage cocktail, and the impact on time taken for catheters to block, as well as levels of crystalline biofilm formation, was measured. In models of established infection, phage treatment significantly increased time taken for catheters to block (∼ 3-fold) compared to untreated controls. However, in models simulating early-stage infection, phage treatment eradicated P. mirabilis and prevented blockage entirely. Analysis of catheters from models of established infection 10 h after phage application demonstrated that phage significantly reduced crystalline biofilm formation but did not significantly reduce the level of planktonic cells in the residual bladder urine. Taken together, these results show that bacteriophage constitute a promising strategy for the prevention of catheter blockage but that methods to deliver phage in sufficient numbers and within a key therapeutic window (early infection) will also be important to the successful application of phage to this problem.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, East Sussex, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Nzakizwanayo
authors.affiliation: Alimentary Pharmabiotic Centre and School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Hanin
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, East Sussex, United Kingdom Blond McIndoe Research Foundation, Queen Victoria Hospital, East Grinstead, United Kingdom Queen Victoria Hospital NHS Foundation Trust, East Grinstead, United Kingdom.
authors.forename: Diana R
authors.initials: DR
authors.lastname: Alves
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, East Sussex, United Kingdom.
authors.forename: Benjamin
authors.initials: B
authors.lastname: McCutcheon
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, East Sussex, United Kingdom.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dedi
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, East Sussex, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Salvage
authors.affiliation: East Surrey Hospital, Surrey and Sussex NHS Healthcare Trust, Redhill, Surrey, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Knox
authors.affiliation: East Surrey Hospital, Surrey and Sussex NHS Healthcare Trust, Redhill, Surrey, United Kingdom.
authors.forename: Bruce
authors.initials: B
authors.lastname: Stewart
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, East Sussex, United Kingdom Blond McIndoe Research Foundation, Queen Victoria Hospital, East Grinstead, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Metcalfe
authors.affiliation: Novolytics Ltd., Daresbury Science and Innovation Campus, Warrington, United Kingdom.
authors.forename: Jason
authors.initials: J
authors.lastname: Clark
authors.affiliation: School of Pharmacy, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Gilmore
authors.affiliation: Alimentary Pharmabiotic Centre and School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Cormac G M
authors.initials: CG
authors.lastname: Gahan
authors.affiliation: Department of Chemistry, University of Bath, Bath, United Kingdom.
authors.forename: A Toby A
authors.initials: AT
authors.lastname: Jenkins
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, East Sussex, United Kingdom Queen Victoria Hospital NHS Foundation Trust, East Grinstead, United Kingdom b.v.jones@brighton.ac.uk.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Jones
mesh_terms: D001435:Bacteriophages / Q000302:isolation & purification / Q000472:pathogenicity*; D018441:Biofilms / Q000254:growth & development; D002408:Catheters, Indwelling / Q000382:microbiology; D004322:Drainage; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D000071059:Phage Therapy / Q000379:methods*; D011512:Proteus Infections / Q000628:therapy*; D011513:Proteus mirabilis / Q000821:virology*; D014546:Urinary Catheterization / Q000009:adverse effects*; D062885:Urinary Catheters / Q000382:microbiology*