Prof Les Baillie
Miss Jennifer Hawkins BSc (October 2011- October 2013)
A joint project between the Welsh School of Pharmacy, Cardiff University and the National Botanical Gardens of Wales. Sponsored by the Knowledge Economy Skills Scholarships (KESS).
Apothecary Bees, Using the honey bee as a tool for drug discovery
The earliest evidence of humans collecting honey is a cave-painting in Valencia, on Spain's eastern coast, thought to date from around 8000 BC. Since about 4000 BC, the ancient Hindi medical theory of Ayurveda outlined honey's medicinal qualities in treating burns, allergies and infections. Western cultures have eventually caught up by devising honey-based wound dressings and oral medicines. But the composition of honey varies greatly, and it depends on the local flora in the bees' immediate environment. With the various flowers bees visit making honey with different healing properties the scope for finding new uses for honey is vast. At Cardiff University I will be carrying out research in order to see if honey can help fight hospital acquired “superbugs”, the deadly bacteria that have developed resistant to conventional antibiotics.
My study will make use of samples provided by honey-makers across the country along with a list of plants near their beehives. Raw, unprocessed samples will be vigorously screened using tests developed over the course of the three years. These tests which include agar diffusion, broth dilution and time-kill assays will be used to identify the honeys with the most activity. The KESS funded project will involve testing the effects of honey against two of the most common hospital acquired infections antibiotic-resistant bacteria MRSA and Clostridium difficile.
DNA profiling will then be carried out in order to identify the plants which contributed to the most powerful honeys. I will see which honeys have the best results against infectious diseases that affect humans and bees and use DNA bar-coding to identify the plants making the honey. This will be done using a DNA-based identification method developed by the National Botanic Garden. The DNA-based method is a pioneering technique which has been made possible due to the recent developments of the The Barcode Wales project. The Barcode Wales project has produced a template DNA barcode for each of the 1143 flowering plants in Wales which is used as a worldwide standard database. Studying the composition and the origin of honey is an exciting area of research, which will be one of the first applications that makes use of this fantastic resource. Once the most potent honeys have been identified in Cardiff I will then investigate the plants found in them. This will allow the identification of the source of the antibacterial properties.
Another focus of the research is to try to find honeys with plant constituents that could help bees to resist pests such as the Varroa mite, which has ravaged the UK bee population, and American foulbrood, a destructive infectious disease that attacks bee larvae throughout the world.
Natural products have been the single most productive source of leads for the development of drugs. As more and more bacteria are becoming resistant to antibiotics the need for new therapeutics is evident. Honey therefore is being used for its potential to develop new drugs.
Mr William McCully MRPharmS (January 2010-January 2013)
A joint project between the Welsh School of Pharmacy, Cardiff University and the National Botanical Gardens of Wales. Sponsored by the KESS program.
A Natural Therapeutic for the Hospital Based Pathogen Clostridium Difficile
Tea is a hot water infusion of the leaves from the Camellia sinensis plant. It is one of the most widely consumed drinks worldwide and in the UK we drink more cups of tea per head than any other nation. There are many different varieties of tea, the most common being black tea and green tea. However, these different varieties are all from the same plant and only differ by the manner in which the plucked leaves are processed.
For centuries tea has been widely used for its medical properties, particularly in Chinese medicine. In recent scientific research tea has been shown to have antibacterial, anticancer and antiviral properties. These properties are thought to be due to a group of antioxidants in tea called polyphenols. Recently at the Welsh School of Pharmacy we discovered that tea inhibits the growth of the hospital ‘superbug’ Clostridium difficile.
The aim of my project is to try and discover what components in tea are responsible for its antibacterial activity against Clostridium difficile and to understand its mechanisms of action. I will also try to modify the growth conditions of a small plantation of Camellia sinensis plants currently housed at the National Botanical Gardens of Wales to produce a ‘super tea’ rich in polyphenols and high in antibacterial activity. We hope to be successful in producing a naturally enhanced tea that will be clinically effective against Clostridium difficile infection.
Mr James Blaxland BSc (January 2011-Dec 2013)
A joint project between the Welsh School of Pharmacy, Cardiff University and ProTEM Services
Hops as a potential treatment for bovine tuberculosis and greenhouse gases
My project is concerned with the disease tuberculosis, Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and is responsible for more deaths than any other single bacterium, a close relative Mycobacterium bovis is responsible for bovine tuberculosis the animal equivalent, which in some cases can spread to humans through contaminated milk products. The disease threatens agricultural production and can have a dramatic effect on food supplies and rural communities in Wales and the rest of the UK, the Welsh assembly government recently released statistics showing that the cost to the taxpayer in compensation to cattle keepers has topped £100 million in the last 10 years. Indeed, the Welsh rural affairs minister Elin Jones showed that between January and October 2010, 6,587 cattle were slaughtered in Wales because of bovine TB.
A possible solution to this problem is by supplementing the animals feed with hops. Hops are known to be antibacterial; their main reason for being in beer is to act as a preservative, and they are known to contain a range of antibacterial compounds which could be used to increase the resistance to the disease in cattle.
Cattle also account for 15-20% of the methane found within the atmosphere and it has been shown that some of the compounds within hops have an antibacterial effect against the bacteria responsible for the production of this methane. The main aims of my project are to identify and purify the active antimicrobial products of hops, with the aim of reducing the impact of bovine TB and greenhouse gases around the world.
Miss Harsha Siani BSc (October 2008-Sept 2011) email: SianiH@cardiff.ac.uk
A joint project between the Welsh School of Pharmacy, Cardiff University and IQ Corporation NL to develop an antibody based therapy for Clostridium difficile
Clostridium difficile has emerged as the most frequent cause of nosocomial diarrhoea, costing the US health care system $1 billion annually and the NHS £4000 to treat per case. The estimated annual healthcare cost of C. difficile associated diarrhea (CDAD) to Wales exceeds £10 million. More disturbing than the economic impact of the infection is the global year-on-year rise in the number of CDAD cases, and the emergence of a new hypervirulent strain responsible for large outbreaks of increased severity in Europe and North America.
Administration of broad spectrum antibiotics disrupts the normal colonic microflora, providing C. difficile with an ecological niche where it can proliferate. The current treatment of choice is metronidazole or oral vancomycin which have been shown to effectively relieve symptoms. However recent reports have indicated an increasing rate of treatment failures, with 15-20% of patients relapsing with 2-8 weeks of discontinuing therapy. This coupled with the risk of vancomycin resistant Enterococci and the potential emergence of metronidazole resistant organisms has resulted in an urgent need to develop new therapeutics. Therapeutics currently in development include new antibiotics, probiotics, vaccines and novel approaches such as faecal transplant.
Studies have shown the ability to mount a robust antibody based immune response plays a key role in mediating protection. Our current research is focused on identifying the immunodominant epitopes of the major virulence factors of C. difficile. Toxin A and Toxin B have been identified as the primary virulence factors, the C terminal region in these toxins have been shown to stimulate production of protective antibodies in animals. Other factors shown to induce the production of antibodies are cell surface associated S layer proteins. Identification of dominant epitopes in these virulence factors will underpin the development of an antibody based assay with which clinicians will be able to identify individuals likely to succumb to recurrent episodes due to a sub-optimal immune response. This approach will also enable us to identify toxin neutralising antibodies.
Miss Lovleen Tina Joshi BSc (October 2008-Sept 2011)
The aim of this PhD is to design an assay for detection of Clostridium difficile spores and vegetative cells within >60 seconds in the faeces of hospitalised patients. There are currently few detection methods that rapidly detect C. difficile’s two toxins with both high specificity and sensitivity. Thus the proposed diagnostic device will detect both virulence toxins A and B in the organism using the novel platform technology of Microwave- Accelerated Metal-Enhanced fluorescence (MAMEF). This will be achieved by identifying conserved genetic signatures from the two toxins and engineering them into the detection assay. The detection device will aid clinicians in diagnosis and treatment of patients with C. difficile infection and those patients with the potential to develop infection.
Mr Abdullah Alyousef MSc (April 2009- March 2012)
The isolation and characterization of lytic bacteriophages for the treatment of Clostridium difficile.
Bacteriophages (viruses the specifically target bacteria) have been successfully used for decades in the former Soviet Union to treat infectious diseases, often in preference to antibiotics. In contrast western countries have traditionally employed antibiotics to treat similar infections and as a consequence we have seen the emergence of micro-organisms such as Methicillin resistant Staphylococcus aureus (MRSA) which are resistant to the majority of commercially available drugs. The problem of drug resistant super-bugs in our hospitals has prompted researchers to look again at the utility of employing bacteriophages (phages) to treat infections caused by these organisms.
We propose to identify phages capable of targeting and inactivating Clostridium difficile, the causative bacterial agent of a debilitating gastric infection of hospitalized patients which has been responsible for significant morbidity and mortality amongst patients in Wales. The estimated annual healthcare costs of C.difficile associated diarrhoea (CDAD) to Wales exceeds £10 million with the highest numbers reported from general and geriatric medical specialties. While the use of certain antibiotics is known to trigger infection, a contributing factor to the increased incidence amongst hospitalized patients has been the ability of the bacterium to form spores which enable the organism to remain viable for many months on contaminated hospital surfaces event following detergent-based cleaning. A 1996 study reported 20% of environmental samples taken from Cardiff hospital wards were positive for C. difficile. This is an important observation given that environmental isolates have been incriminated in the spread of CDAD via healthcare personnel hands.
The ability to treat critically ill individuals and to decontaminate their immediate environment and thus prevent the spread of infection to fellow patients would have a significant impact on healthcare outcomes and ultimately costs. Phages offer a number of advantages which include safety, they are one of the commonest life forms on the planet with a long history of safe use in humans, specificity in that they target a single type of microorganism leaving other beneficial bacterial untouched and finally they have activity against antibiotic resistant strains.
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- Katie Brenneman. Interaction of anthrax toxin components
- Matt Bell. Molecular triggers of the innate immune system
- Caroline Redmond. Characterization of the exosporium of Bacillus Anthracis
- Rachel Williams. Development of molecular tools for the functional and comparative analysis of avirulent Bacillus anthracis UM23CL-2
- Joanne Thwaite. Studies on the expression of Bacillus anthracis Protective antigen from Bacillus subtilis
- Mark Rees. Development of Bacillus sp for the efficient export of Bacillus anthracis protective antigen
- Kate Fowler. Humoral and cell mediated vaccine-induced protection against infection with Bacillus anthracis
- Billy Shaw. Development of method to characterize the human immune response to the UK licensed anthrax vaccine