N. Holling Approaches to control infection, encrustation, and blockage of urinary catheters

This project now redirects to Pure

https://research.brighton.ac.uk/en/projects/approaches-to-control-infection-encrustation-and-blockage-of-urin

established December 2023

 

 

A wide range of bladder conditions in elderly individuals are managed using long-term catheterisation, and this simple strategy usually provides substantial improvements in quality of life. However, these benefits are frequently undermined by infections. The bacterial species Proteus mirabilis is a particular problem in this regard, and often causes blockage of catheters, which leads to other serious complications.

Presently, there are no approaches that provide good control of these infections, and effective strategies are urgently needed. Based on our previous work we have shown that specialised components of the P. mirabilis cell, which act like “pumps” and referred to as efflux systems, are important to the ability of P. mirabilis to infect and block catheters. 

Project aims

The overall aim of this project is to determine if chemical inhibition of efflux systems in P. mirabilis can prevent or reduce catheter blockage. The impact of efflux inhibition on susceptibility to antibiotics commonly used to treat UTI, and the potential for synergistic EPI: antibiotic treatment will also be explored, as well as the use of EPIs for prevention of biofilm formation in a range of other common uropathogens.

Project findings and impact

In the UK alone, around 3.2 million individuals over the age of 65 are incontinent. It is estimated that as many as 200,000 may undergo long-term help to manage this condition, and up to 40 per cent of older people in residential care undergo long-term urethral catheterisation. As the aged population grows this figure will continue to rise.

Associated infections are linked with increased morbidity and mortality as well as spread of antibiotic resistance, and a significant financial burden to the NHS (~£123 million p.a.). Proteus mirabilis is a particular problem in this regard, implicated in over 40 per cent of cases, and leads to chronic infections with serious complications.

The development of effective countermeasures against such infections will have a considerable positive impact on the wellbeing of many older people, and provide substantial savings for the NHS. Because many drugs already in clinical use are potential inhibitors of bacterial efflux systems (EPIs), confirming the efficacy of such EPIs for controlling catheter infections has clear potential to provide an effective intervention within 5-10 years.

Research team

Dr Brian Jones

Dr Jonathan Nzakizwanayo

Output

N. Holling, D. Lednor, S. Tsang, A. Bissell, L. Campbell, J. Nzakizwanayo, C. Dedi, J. A. Hawthorne, G. Hanlon, L. A. Ogilvie, J. P. Salvage, B. A. Patel, L. M. Barnes and B. V. Jones* (2014). Elucidating the genetic basis of crystalline biofilm formation in Proteus mirabilis. Infection and Immunity, 82: 1616-1626

Holling N., Dedi C., Jones C. E., Hawthorne J. A., Hanlon G., Salvage J. P., Patel B. A., Barnes L. M., Jones B. V.* (2014) Evaluation of environmental scanning electron microcopy in conjunction with energy dispersive x-ray spectroscopy for analysis of crystalline biofilms. FEMS Microbiology Letters, 355: 20-27.

Savory N., Lednor D., Tsukakoshi K., Abe K., Yoshida W., Ferri S., Jones B. V*., Ikebukuro K. (2013) In silico maturation of binding-specificity of DNA aptamers against Proteus mirabilis. Biotechnology and Bioengineering,110:2573-80.

Partners

Queen Victoria Hospital NHS Foundation Trust

Queen Victoria Hospital Charitable Trust

Blond McIndoe Research Foundation