Scientists debug Clostridium difficile

Mar 2 2009

An international team of scientists, led by Monash University researchers, has uncovered the workings of a superbug that kills elderly hospital patients worldwide - a discovery that has the potential to save lives and health care systems billions of dollars each year.

The research published today in the prestigious scientific journal Nature, unravelled ways to genetically modify the bacterium Clostridium difficile and solved the mystery surrounding its toxicity.

Professor Julian Rood from the Department of Microbiology and lead author, microbiologist Dr Dena Lyras, made a major scientific breakthrough which allowed mutants of the superbug to be made. They then identified which of two suspected toxic proteins was essential for the bacterium to cause severe disease.

"Contrary to previously accepted scientific belief, our results show that toxin B, which was considered the less important toxin is actually the toxin that causes disease," Professor Rood said.

"This discovery will lead to new methods for the control and prevention of this disease".

Professor Rood and Dr Lyras have been working toward this result for more than a decade. Dr Lyras said strains of Clostridium difficile are found in almost every hospital in Australia.

"It is the major cause of diarrhoea in hospital patients undergoing antibiotic therapy. The antibiotics destroy the 'good' bacteria in the gut, allowing a 'bad' bacterium to grow in the colon, where it causes a chronic bowel infection that is very difficult to treat," Dr Lyras said.

"The disease produces two types of Toxins, known as A and B. Worldwide research has tended to focus on these purified toxins in isolation from the bug. This only resulted in part of the story being told. We took a big picture approach and through genetic modification of the bug, together with infection studies with our US collaborators, we were able to see the whole picture," Dr Lyras said.

Statistics show that in the US, more people die from Clostridium difficile infections than all other intestinal infections combined, with most deaths involving patients aged 65 years or over. The disease is believed to have contributed to more than 8,000 deaths in the UK in 2007. A less aggressive form of the bacteria is present in Australia but statistics in 1995-dollars show the cost of managing the disease to be around $1.25 million dollars per hospital, per year.

Their research lays the foundation to find better ways to treat the superbug.

"We are now beginning to understand the workings of the superbug, which allows us to work on treatments for it. We are confident our research will pave the way for future drugs to try to wipe out this disease. I can't put a time frame on how quickly drugs could be developed, but we're certainly on that road to discovery," Dr Lyras said.