C diff adapting to spread more easily in hospital settings

They found Clostridium difficile – commonly referred to as C difficile or C diff – has evolved into two separate species with one highly adapted to spreading in hospital wards.

“Ultimately, this could help us understand how other dangerous pathogens evolve”

Brendan Wren

An emerging species of the bacteria named Clade A was found to make up 70% of samples taken from hospital patients, according to findings published in the journal Nature Genetics.

Researchers from the Wellcome Sanger Institute, London School of Hygiene and Tropical Medicine and collaborators identified genetic changes that allow this species to thrive on a sugar-rich Western diet, evade standard hospital disinfectants and spread easily.

They said their research – said to be the largest ever genomic study of C difficile – shed new light on the way that bacteria develop and could help inform efforts to prevent and control infection.

C difficile can live harmlessly in the gut where it is kept under control by “good” bacteria. However, taking antibiotics can wipe out this natural protection, allowing C difficile to infect the gut.

As well as debilitating diarrhoea, the bacteria can cause bowel inflammation and is often difficult to treat, mainly affecting elderly and vulnerable patients. Infections can be fatal.

“Our study provides genome and laboratory-based evidence that human lifestyles can drive bacteria to form new species”

Trevor Lawley

Frequently found in hospitals, C difficile forms resistant spores that allow it to remain on surfaces and spread easily between people.

While the NHS has made great strides in reducing C diff cases, the rate of improvement has slowed in recent years.

National regulations mean trusts must report cases and face financial penalties sanctions if they fail to meet targets set for their organisation.

The latest monthly data from June this year shows that NHS acute trusts reported a total of 1,065 cases, with 420 infections contracted in hospital.

To understand how the bacteria was evolving, the researchers collected and grew more than 900 different strains found in humans, animals and the environment.

By sequencing the DNA of each strain and comparing and analysing the genetic sequences – or genomes – they discovered C difficile was evolving into two different species.

“Our large-scale analysis allowed us to discover that C difficile is currently forming a new species with one group specialists to spread in hospital environments,” said Dr Nitin Kumar joint first author from the Wellcome Sanger Institute.

“This emerging species has existed for thousands of years but this is the first time anyone has studied C difficile genomes in this way to identify it,” he added.

Dating analysis revealed C difficile Clade A first appeared about 76,000 years ago and the number of strains started to increase at the end of the 16th Century before modern hospitals existed.

Since then the group has gone on to thrive in hospital settings with many strains that keep adapting and evolving, the study found.

Studies of C difficile in mice found the emerging species thrived on a sugar-rich diet. Meanwhile, differences in genes involved in forming spores made it much more resistant to common hospital disinfectants.

Dr Trevor Lawley, senior author from the Wellcome Sanger Institute, said the findings showed the bacteria was continuing to evolve in response to human behaviour including advances in infection control.

“Our study provides genome and laboratory-based evidence that human lifestyles can drive bacteria to form new species so they can spread more effectively,” he said.

“We show that strains of C difficile bacteria have continued to evolve in response to modern diets and healthcare systems and that focusing on diet and looking for new disinfectants could help in the fight against this bacteria.”

Professor Brendan Wren, from the London School of Hygiene and Tropical Medicine, said the study, which involved looking at C difficile genomes from 33 different countries, “gives us a whole new understanding of bacterial evolution”.

“Ultimately, this could help us understand how other dangerous pathogens evolve by adapting to changes in lifestyle and healthcare regimes, which could then inform healthcare policy,” he said.