Secrets of severe gastro-bug revealed
An international team of scientists has turned current wisdom about the leading cause of infectious diarrhoea in hospitals on its head.
The researchers say the findings will ensure less misdiagnosis of people infected with the bacteria, Clostridium difficile.
Diseases caused by Clostridium difficile flourish when people are given antibiotics or their normal gastrointestinal flora is reduced.
This allows the bacteria to invade the gut and release toxins that cause severe diarrhoea and gastrointestinal disease.
"This bug takes advantage when antibiotics kill everything else in our bodies," says Lyras.
The bacteria releases two toxins, and until now, scientists have diagnosed infection by C. difficile-associated disease by testing for one of them, Toxin A, which was believed to be the main cause of symptoms.
But tests of bacteria obtained from sick people showed about 3% of the bacteria did not produce Toxin A.
However, all had Toxin B.
The results provide direct evidence that Toxin B is the main culprit behind C. difficile-related illness, overturning our 30-year understanding of how this bug causes disease with implications for diagnosis and treatment.
Genetically engineered bacteria
Lyras says previous studies had tested the effect on animals of Toxin A and Toxin B extracted from C. difficile.
But she and colleagues took quite a different approach. They infected animals with two genetically engineered versions of C. difficile - one producing only Toxin A, the other producing only Toxin B.
Lyras says testing the whole bacteria in animals is essential to reflect what happens in the real world.
"It's like when you take a cog out of a machine. You can look at that cog and try to figure out what it's doing but it's only when you put it back in the context of the whole machine that you see how the whole machine runs together," she says.
To produce the two forms of C. difficile, the researchers synthesised a neutral piece of DNA that was able to be inserted into the bacteria and replace (knock out) either the Toxin A or Toxin B gene.
In animal tests carried out in the US, the researchers found that only the bacteria that produced Toxin B was still able to cause disease.
"The bugs that just make Toxin A don't make the animal sick at all, whereas the bugs that make only Toxin B actually kill the animal within three days," says Lyras.
Lyras says the findings mean diagnosis of C. difficile-associated disease will now focus on the presence of Toxin B rather than Toxin A.
Previously diagnosis relied on testing for Toxin A and this led to many infected people being misdiagnosed as free of the disease, she says.
The findings also mean research efforts to find alternative treatments to antibiotics, such as vaccines, will also need to refocus on Toxin B.
Lyras says currently most people affected by C. difficile are aged over 65 and the associated disease is very difficult to treat.
To add to this is the threat of superbugs that produce more toxin and are resistant to most antibiotics, affecting a wider range of people.
In the US, 1997 estimates suggest C. difficile superbugs cost the country US$3.2 billion a year in extra costs, says Lyras.
"This is a bug that needs to go on our radar," says Lyras. "If the superbug gets to Australia this is going to cost our healthcare system a lot of money."