Our research focuses on microbiological issues related to human health. The three main areas are:
- Hospital-acquired infections
- Bacteriophage as antimicrobial agents, preventing immune cell activation
- How antimicrobial products like biocides work
Additional projects:
- Monitoring water microbial activity
- Gut bacteria and human health
- Use of activated carbon filters to remove toxins
The role of bacterial adhesion in the pathogenesis of device-related infections
If bacteria are allowed to colonise the surface of an implanted device, they develop into biofilms (structured consortia of cells exhibiting profound antibiotic resistance). These biofilms are virtually impossible to eradicate and act as a reservoir for persistent bacterial infection. The major problem associated with implanted medical devices is infection as a result of this natural tendency of bacteria to colonise surfaces. Such infections are invariably hospital-acquired, and up to one half of the episodes of nosocomial endocarditis recorded have been traced to infected intravascular catheters, with a mortality rate of 50%. In addition, millions of urinary catheters are used each year in the UK and the majority of these will become infected. Catheter-associated urinary tract infections are the second most common cause of nosocomial bloodstream infections. The main focus of our work has been an examination of the initial adhesive events (including cell and substratum surface characterisation), development of in vitro models to mimic the in vivo situation and evaluation of strategies to minimise adhesion. Our strategies have included chemical modification of the implant surface to impede attachment and the incorporation of biocides either directly onto the surface or embedded within polymeric coatings. These projects have been funded by industry (Biocompatibles) and the research councils.
Bacteriophage technology
The emergence of bacteria resistant to most, if not all, of the commonly used antibiotics has prompted the search for alternative treatment strategies. Bacteriophages (phages) are viruses that only attack bacteria but have a defined specificity such that a given phage will only attack a single species, or in some cases, a particular strain of bacterium. They cannot infect mammalian cells and so are harmless to humans. When a lytic bacteriophage encounters its bacterial host it binds, using specific receptors present on the tail fibres, to specific components on the cell surface. The phage genome is then injected into the host cell where it essentially hijacks the metabolic machinery of the bacterium to act as a factory for the production of new virus particles, destroying the host bacterial cell in the process. Although the discovery of bacteriophages predates that of antibiotics, their use in therapy was sidelined with the success of antibiotics. We are investigating the use of bacteriophages as antimicrobial agents against Pseudomonas aeruginosa, which is a common pathogen in patients with cystic fibrosis. In the course of infection the bacterium forms a tenacious biofilm in the airway of the patient and the prognosis is poor. The project attempts to understand the interplay between airway epithelial cells, bacterial biofilm and bacteriophage by growing co-cultures of these cells and monitoring cytokine release in response to phage administration. Other pathogens under investigation include Acinetobacter baumannii (which is highly antibiotic resistant and a frequent contaminant in burns patients), Staphylococcus aureus (particularly MRSA) and Clostridium difficile. These investigations are being conducted in collaboration with scientists from the Eliava Institute of Bacteriophage, Microbiology and Virology in Tbilisi, Republic of Georgia and are funded by the EU via INTAS.
We are also the co-ordinator on a multi-partner European Commission funded FP7 project, BATCIC, which is investigating the use of bacteriophages to treat urethral catheter infections.
Mode of action of biocidal agents
A wide range of biocidal agents are used as preservatives, disinfectants, and antiseptics. Most of these have been in use for many years, yet very little is known about their precise mode of action. This has become of particular importance as the costs of bringing a new product to market escalate and manufacturers look to reformulate existing compounds to provide synergistic effects. We have acquired a great deal of experience in investigating the mode of action of biocidal agents and used our expertise to design mathematical models which predict the antimicrobial efficacy of biocides in combination. This is proving invaluable in allowing the rational approach to the formulation of antimicrobial products. We have combined this expertise with our knowledge of biofilms to create models predicting the efficacy of biocides on surfaces contaminated with microorganisms. Our approach has been used to evaluate the use of ortho-phthalaldehyde in the high-level disinfection of soiled endoscopes. In addition we are exploring the use of photoactivated disinfection, using a dye solution activated by laser light, as a means of eradicating biofilms from the surface of implanted medical devices. This has proved highly successful in disinfecting infected root canals in dentistry. These projects are funded by industry including Reckitt Benckiser, Procter and Gamble, Johnson and Johnson, and Denfotex.
We are also involved in several additional projects:
Advanced monitoring and control of microbial water quality (AMACOM)
This project was funded by the European Community under its Interreg IIIA programme. The purpose was to form a collaborative partnership between research centres based at the University of Brighton (School of Pharmacy and Biomolecular Sciences, together with School of the Environment), the University of Rouen and CNRS in Rouen. The research institutions are supported by Southern Water Scientific Services, Falmer, UK (also Kent Laboratory, Chatham, UK) in providing the community with a better understanding of the ecology of microorganisms in the bathing and drinking waters of the Euro-Region.
The partners in this project had not worked together previously and so the Interreg IIIA programme represented a unique opportunity to combine complementary expertise within the Region. The scientific objectives of the project are as follows:
- To evaluate the environmental sources and sinks of faecal bacteria in surface waters and determine the prevalence of Legionella pneumophila in domestic and industrial water supplies of the Euro-Region.
- To establish a library of characterised environmental bacterial isolates and their respective bacteriophages in order to validate the advanced detection and prediction tools developed.
- To monitor and evaluate the effectiveness of water disinfection systems against contaminant bacterial biofilms.
- To develop and evaluate a rapid microbial monitor for the assessment of water quality using bacteriophages as the bioselective detection sensor system.
- To determine the effect of geographical and temporal variations on the classification of water quality within an urban and maritime Euro-Region using GIS technology.
Role of gut microbiota in human health
This research is focused on understanding the impact of the human gut microbiota in health and disease and elucidating the core functions of this community through metagenomic and other culture-independent approaches. The study of this ecosystem encompasses many themes including microbial pathogenesis, host-microbe and microbe-microbe interactions, molecular microbial ecology, horizontal gene transfer and bacterial evolution and adaptation.
The human gut microbiota comprises more than 1000 predominantly uncultured bacterial species. The population density is approximately 1014 cells in the colon and collectively this community is estimated to encode over 100 times the number of genes present in the human genome. In addition to potential roles in several major diseases of the gut such as colorectal cancer, Crohn’s disease and ulcerative colitis, the activities of this community may also impact on cardiac disease through modulation of cholesterol levels in the host and metabolic diseases such as diabetes. Strong evidence also exists for a key role of the gut microbiota in early human development, and in particular this community is thought to be vital for proper maturation of the developing immune system.
Removal of bacerial toxins by activated carbons
New collaborations with the Biomedical Materials Group are in place to explore the potential of novel activated carbons in the treatment of toxin-mediated disease such as Clostridium difficile colitis (link to biomedical materials)
