University of Nottingham Communications Department

NEWS ARTICLE

Gene technology to fight infection

Mon, 19 Jan 2009 12:27:00 GMT

PA9/09

Scientists at The University of Nottingham are leading a major European study to unravel the genetic code of one of the most lethal strains of hospital acquired infections.

The 3 million euro, three-year study will use gene knock-out technology developed in Nottingham to study the function of genes in a ‘super’ strain of the bacteria Clostridium difficile to discover why it causes more severe disease, kills more people, is harder to eradicate and more resistant to antibiotics.

It is hoped that the HYPERDIFF study, which involves partners from the UK, Slovenia, Italy, France, The Netherlands and Germany and is funded with a grant from the European Community, will lead to better tests to diagnose ‘super’ strains of C.difficile, more effective treatments and, possibly, even a vaccine to protect against the disease.

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Since the turn of the new millennium there has been a dramatic increase in the incidence of C.difficile. Currently the most frequently occurring healthcare associated infection, last year it killed more than seven times as many people in the UK as MRSA. Reasons for this increase may include improvements in reporting procedures, the increasing age of the population as the elderly are especially vulnerable, lower standards of hygiene and overcrowding on hospital wards.

However, a further significant factor has been the arrival in Europe of so-called ‘hypervirulent’ strains such as ribotype 027, which are responsible for more severe disease and are more difficult to treat.

Currently, scientists know that the bacteria cause disease by sticking to epithelial cells of the gut lining and releasing two toxins that damage cells leading to the tell-tale symptom of severe diarrhoea. However, there is very little known about the ways in which the bacteria operate and why the strain should be more severe than its less virulent cousins.

Leading the study, Professor Nigel Minton in The University of Nottingham’s School of Molecular Medical Sciences, said: “These hypervirulent organisms seem to be taking over as the dominant strain in outbreaks and, worryingly, there are only two antibiotics which are still effective against them. There is a very real danger that total resistance may arise, and if that happens then this will become an extremely serious problem.

“The idea behind the study is that we investigate the genomes of the hypervirulent strains and identify their differences to the so-called standard strains. In this way, we should get a clearer picture of the whole range of factors involved in its spread and the way in which it causes disease.”

During the three-year study, scientists at Nottingham will use a technology called ClosTron to produce mutant versions of the hypervirulent strains. They will knock out genes one by one and then compare the mutant version to the standard organism to assess the function of each cell.

The project will also investigate whether pets and other domesticated animals are carriers of the bacteria and what effect this may have had on the rise of C.difficile as a community acquired infection.

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Notes to editors: The University of Nottingham is ranked in the UK's Top 10 and the World's Top 100 universities by the Shanghai Jiao Tong (SJTU) and Times Higher (THE) World University Rankings.

It provides innovative and top quality teaching, undertakes world-changing research, and attracts talented staff and students from 150 nations. Described by The Times as Britain's "only truly global university", it has invested continuously in award-winning campuses in the United Kingdom, China and Malaysia.

Twice since 2003 its research and teaching academics have won Nobel Prizes. The University has won the Queen's Award for Enterprise in both 2006 (International Trade) and 2007 (Innovation — School of Pharmacy), and was named Entrepreneurial University of the Year at the Times Higher Education Awards 2008.

Its students are much in demand from 'blue-chip' employers. Winners of Students in Free Enterprise for four years in succession, and current holder of UK Graduate of the Year, they are accomplished artists, scientists, engineers, entrepreneurs, innovators and fundraisers. Nottingham graduates consistently excel in business, the media, the arts and sport. Undergraduate and postgraduate degree completion rates are amongst the highest in the United Kingdom.

More information about C.difficile can be found on the web at www.clostridia.net

Partners in the HYPERDIFF project are: Professor Maja Rupnik, Institute of Public Health Maribor, Maribor, Sweden; Dr Paolo Mastrantonio, Istituto Superiore di Sanità (The Italian National Institute of Health), Rome, Italy; Professor Anne Collignon. Université Paris Sud XI, Paris, France; Dr Ed Kuijper, Leiden University Medical Centre, Leiden, The Netherlands; Professor C. von Eichel-Streiber, tgcBIOMICS GmbH, Mainz, Germany; Professor Peter Mullany, University College London, Eastman Dental Institute, London, UK.