Abstract

Proteus mirabilis is an enterobacterium that causes catheter-associated urinary tract infections (CAUTIs) due to its ability to colonize and form crystalline biofilms on the catheters surface. CAUTIs are very difficult to treat, since biofilm structures are highly tolerant to antibiotics. Phages have been used widely to control a diversity of bacterial species, however, a limited number of phages for P. mirabilis have been isolated and studied. Here we report the isolation of two novel virulent phages, the podovirus vB_PmiP_5460 and the myovirus vB_PmiM_5461, which are able to target, respectively, 16 of the 26 and all the Proteus strains tested in this study. Both phages have been characterized thoroughly and sequencing data revealed no traces of genes associated with lysogeny. To further evaluate the phages’ ability to prevent catheter’s colonization by Proteus, the phages adherence to silicone surfaces was assessed. Further tests in phage-coated catheters using a dynamic biofilm model simulating CAUTIs, have shown a significant reduction of P. mirabilis biofilm formation up to 168 h of catheterization. These results highlight the potential usefulness of the two isolated phages for the prevention of surface colonization by this bacterium.

Highlights

  • Indwelling urinary catheters are medical devices used by millions of people to relieve urinary retention and urinary incontinence

  • Reference strains were obtained from Salmonella Genetic Stock Centre (SGSC) and Colección Española de Cultivos Tipo (CECT), while isolates were obtained from Laboratório de Análises Clínicas

  • Bacteria were grown at 37◦C in Tryptic Soy Broth (TSB; Liofilchem), on Tryptic Soy Agar (TSA; 1.5% agar) or in Artificial Urine (AU) (Brooks and Keevil, 1997) supplemented with 0.3% glucose (Silva et al, 2010)

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Summary

Introduction

Indwelling urinary catheters are medical devices used by millions of people to relieve urinary retention and urinary incontinence. Despite the important benefits brought by the use of these devices, catheters provide a suitable surface for the colonization of microorganisms and may further place at risk the patients’ health, due to infections. In USA, catheter-associated urinary tract infections (CAUTIs) account for up to 40% of hospital-acquired infections (Saint et al, 2008). 70% of urinary tract infections (UTIs) are associated with urinary catheters (Burton et al, 2011; Weber et al, 2011) and approximately 20% patients will suffer a catheterization during their hospital stay, especially in intensive care units (Saint and Lipsky, 1999).

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