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Issue 27, 2017
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Prevention of encrustation and blockage of urinary catheters by Proteus mirabilis via pH-triggered release of bacteriophage

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Abstract

The crystalline biofilms of Proteus mirabilis can seriously complicate the care of patients undergoing long-term indwelling urinary catheterisation. Expression of bacterial urease causes a significant increase in urinary pH, leading to the supersaturation and precipitation of struvite and apatite crystals. These crystals become lodged within the biofilm, resulting in the blockage of urine flow through the catheter. Here, we describe an infection-responsive surface coating for urinary catheters, which releases a therapeutic dose of bacteriophage in response to elevated urinary pH, in order to delay catheter blockage. The coating employs a dual-layered system comprising of a lower hydrogel ‘reservoir’ layer impregnated with bacteriophage, capped by a ‘trigger’ layer of the pH-responsive polymer poly(methyl methacrylate-co-methacrylic acid) (EUDRAGIT®S 100). Evaluation of prototype coatings using a clinically reflective in vitro bladder model system showed that catheter blockage time was doubled (13 h to 26 h (P < 0.05)) under conditions of established infection (108 CFU ml−1) in response to a ‘burst-release’ of bacteriophage (108 PFU ml−1). Coatings were stable both in the absence of infection, and in the presence of urease-negative bacteria. Quantitative and visual analysis of crystalline biofilm reduction show that bacteriophage constitute a promising strategy for the prevention of catheter blockage, a clinical problem for which there is currently no effective control method.

Graphical abstract: Prevention of encrustation and blockage of urinary catheters by Proteus mirabilis via pH-triggered release of bacteriophage

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Publication details

The article was received on 12 May 2017, accepted on 22 Jun 2017 and first published on 22 Jun 2017


Article type: Paper
DOI: 10.1039/C7TB01302G
J. Mater. Chem. B, 2017,5, 5403-5411
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    Prevention of encrustation and blockage of urinary catheters by Proteus mirabilis via pH-triggered release of bacteriophage

    S. Milo, H. Hathaway, J. Nzakizwanayo, D. R. Alves, P. P. Esteban, B. V. Jones and A. T. A. Jenkins, J. Mater. Chem. B, 2017, 5, 5403
    DOI: 10.1039/C7TB01302G

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