Dr Nigel Minton
This profile is taken from the MRC Annual Review 10/11, Perspectives, which tells the stories of MRC scientists who made some of the most compelling research discoveries of 2010/11 by thinking about research problems from a new angle.
Professor of applied molecular microbiology at the University of Nottingham.
With MRC funding, Professor Nigel Minton has made an important discovery about the hospital-acquired infection C. difficile.
Nigel leads a team of researchers dedicated to studying a group of bacteria called Clostridia. He jokingly badges himself as a “Clostridia fanatic” and when he describes the wide range of potential uses for these bacteria, it’s easy to see why he is so enthusiastic.
“They’re a fantastic group of organisms and I always say that the antics of a few give the rest a bad name. Of the 100 or so Clostridia species only about 12 cause diseases. But there are all these other wonderful Clostridia that can do amazing things – we can use them to make biofuels, they can selectively destroy tumour tissue and treat cancer, and they can even be genetically modified to make aviation fuel. But at the same time, some Clostridia can cause serious health problems, and I am determined to do something about that by understanding more about how pathogenic Clostridia infect their hosts.”
Lurking in hospitals
One species, Clostridium difficile (C. difficile) is a major public health problem, causing healthcare-acquired infections. In 2008/09, C. difficile was responsible for over 4,000 deaths in UK hospitals, four times more than the number who died from MRSA infection.
“Most people don’t realise that it’s actually a bigger problem than MRSA,” says Nigel. “C. difficile is principally a disease of the elderly. When older people go into hospital and are given antibiotics, the normal beneficial bacteria within the gut are disrupted, and if C. difficile is around it takes over the gut, and can cause severe, explosive diarrhoea and produces spores – dormant seeds – which spread around the hospital.
“It causes greatest devastation in the elderly and until recently the UK had the highest infection rates it the world, so there have been major strides in recent years by the NHS to reduce infection rates, and fortunately the incidence of C. difficile is now starting to come down.”
Nigel and his research team have developed genetic tools to study C. difficile to try and understand all the different components of the bug that contribute to how it infects people.
“For any disease, bacterial infection or otherwise, in order to understand the individual factors that contribute, you need to look at what happens when it isn’t there. That’s really how you find out what the products of different genes do and how they affect virulence. Until recently, it was practically impossible to genetically manipulate C. difficile, so that was the driving force behind setting up my research group and we’ve now developed some very efficient systems.”
Overturning preconceptions
Nigel explains that C. difficile causes severe diarrhoea by producing two powerful toxins, toxin A and toxin B, which cause damage to the lining of the gut. For a long time, scientists believed that toxin A was the more important factor in causing disease. This appeared to be confirmed definitively in 2009 with the publication of a high profile paper which showed that a version of C. difficile that had been genetically manipulated to produce only toxin B caused diarrhoea in hamster model, and that a version which could produce only toxin A did not.
But around the same time, Nigel’s group were doing similar experiments, and their results were very different: “With our MRC funding we were making mutants with a more efficient technology which were more stable. In direct contrast to the findings of the other group, our bacterium which had only toxin A did cause diarrhoea.
Toxin targeting
“Our finding is really important because there are a lot of companies out there looking to develop drugs that protect against C. difficile by targeting the toxins. The study that preceded ours gave them the message that they possibly didn’t need to bother making drugs or diagnostic kits which targeted toxin A because it wasn’t important – but our finding showed that this wasn’t the case, and re-directed attention of companies back to toxin A.”
Nigel and his group are now trying to establish whether additional mutations in the genome of the bacterial strains used in the other study caused the differing results. They have also reproduced the results of their study using a particularly virulent strain of C. difficile which caused major outbreaks at Stoke Mandeville Hospital in Buckinghamshire in 2005 and 2006, causing 36 deaths.
When asked about his motivation for doing research, Nigel gives a straight-talking answer: “I don’t believe in doing research for esoteric reasons – there has to be a reason for doing it, which is why I asked for my professorial title to include the word ‘applied’. The tax payer deserves value for money so there must be output. Perversely, I’ve never believed in focusing on getting the next paper published in a high profile journal, so it’s ironic that we ended up getting this research published in Nature!”
Watch a video of Nigel talking about his work
Published October 2011