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Waging war on the deadliest superbug

04.07.2007
It infiltrates hospitals as microscopic spores. Its defences are so strong it can resist most antibiotics. And it kills three times as many people every year as MRSA. But scientists at The University of Nottingham are amassing an arsenal of weapons in preparation for counter offensive against the most deadly of hospital superbugs.

A research group led by Professor Nigel Minton in the Centre for Healthcare Associated Infections (CHAI), with Dr Peter Mullany at University College, London have been awarded over £1.6m for one of the country’s largest studies into C.difficile (C. diff). The work funded by the Medical Research Council, follows a scientific breakthrough by CHAI microbiologists that is set to revolutionise the genetic analysis of Clostridium difficile and its close relatives.

Until now scientists have understood very little about the biology of C-diff. With funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Morvus Technology Ltd, Professor Nigel Minton and his team have developed the ClosTron “knock out” system which can target specific genes in C. diff and other clostridial species. For the very first time scientists have an extremely rapid and effective way of identifying and deactivating the toxins and other factors that cause the disease and can begin the search for new therapies to prevent or cure it.

Professor Minton said: “Although we have the entire genetic blueprint of C.diff, and have an inkling as to what bacterial factors might be important in disease, we have been unable to test these ideas. You never really know what a particular factor is doing until it isn’t there. You need to be able to inactivate, ‘knock-out’, the gene responsible, and then see if the bacterium can still cause disease. Until now ‘knocking out’ genes has been very difficult to do. Our breakthrough ClosTron technology now makes gene knock-out very quick and easy. Once we know what factors are important we should be able to develop methods of preventing C.diff causing disease”.

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As well as knocking out genes the ClosTron technology can be used to insert them. Professor Minton hopes this will improve their chances of; (i) developing new anti-cancer treatments that are delivered by the spores of harmless clostridial species that target the cancer tissue; (ii) more effectively controlling the food borne bacterium C. botulinum, and (iii) improving the efficiency of the production of the biofuel butanol by C. acetobutylicum using metabolic engineering.

Official figures show that 5000 people die from a healthcare-associated infection every year in the UK and tackling the super bugs costs the NHS £1bn a year. 1 in 12 of us will pick up an infection during a stay in hospital. There’s a 1 in 77 chance of contracting MRSA and a 1 in 50 chance of developing C. diff.

CHAI brings together some of the country’s leading experts in the field of healthcare associated infections. They are about to apply for part of a £16.5m fund set up by the UK Clinical Research Collaborations’ Translational Infection Research Initiative which has acknowledged a lack of funding for research in the field of microbiology and infectious diseases.

As antibiotics become increasingly ineffective in the fight against C.diff and MRSA scientists at CHAI are working on ways of incapacitating the bacteria and leaving the immune system to deal with the infection. This will reduce the selection pressure for antibiotic resistance that arises from the use of traditional antibiotics.

Professor Richard James, Director of CHAI said: “We intend to apply for £5m over the next five years to increase the critical mass of researchers drawn from nine schools at The University of Nottingham who give CHAI its unique breadth of expertise. This funding will be used to investigate an integrated programme of action in hospitals that can reduce the incidence of infections, for new diagnostic tests to rapidly identify C. diff or MRSA and to develop novel antibiotics in order to treat these infections. The success of this research will be judged by both improved patient outcomes and savings to the NHS in the costs of treating infections”.

CHAI was officially launched in December last year as a national research centre to lead the way in the fight against killer super bugs. Its patron is Actress and TV personality Leslie Ash, who almost died and was left virtually paralysed after contracting MSSA, a strain related to MRSA, in a London hospital.

The work carried out by The University of Nottingham in healthcare associated disease will feature on BBC Radio 4 at 9pm on Wednesday 4th July and 11th July when presenter Dr Mark Porter tackles the issue of multi-drug resistance. The two part programme called “Rise of Resistance” features Professor Richard James, Professor Nigel Minton and Professor Paul Williams who will discuss the difficulties related to drug resistance and to their own research and how that might be useful in the future.

Emma Thorne | alfa
Further information:
http://www.nottingham.ac.uk

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