Gene technology to fight Clostridium difficile

Jan 19 2009

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.

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.