An artificial sugar called trehalose enhances the virulence of epidemic lineages of Clostridium difficile, a Gram-positive spore forming bacterium that causes life-threatening inflammation of the colon, according to a new study published in the journal Nature.
This digitally-colorized scanning electron microscopic image depicts a large grouping of rod-shaped Clostridium difficile. Image credit: Janice Carr & Lois S. Wiggs, CDC.
“Clostridium difficile infections have always been a problem in hospitals, but during the last 15 years they have become the most common cause of hospital-acquired infections in developed countries,” said study senior author Professor Robert Britton, of Baylor College of Medicine.
“Our group and others have found that two Clostridium difficile lineages (RT027 and RT078) have become dominant more recently around the globe,” added study first author Dr. James Collins, a postdoctoral researcher at Baylor College of Medicine.
“These lineages have been present in people for years without causing major outbreaks; in the 1980s they were not epidemic or hypervirulent but after the year 2000 they began to predominate and cause major outbreaks. We wanted to know what had helped these lineages become a major health risk.”
According to the team, resistance to fluoroquinolone antibiotics is likely one of the factors that is helping lineage RT027 cause epidemics.
“However, fluoroquinolone resistance is also a characteristic of other Clostridium difficile lineages that are not epidemic,” Dr. Collins said.
“We searched for other factors that would help RT027 and RT078 increase their virulence.”
The authors investigated what sources of food these lineages preferred.
They discovered that RT027 and RT078 can grow on extremely low concentrations of trehalose (also known as mycose or tremalose), an alpha-linked disaccharide used as a sweetener in Australia and Japan.
Each lineage is highly efficient at using trehalose and evolved independent mechanisms to utilize this sugar.
To connect the ability to metabolize low levels of trehalose with increased disease severity, the researchers worked with a mouse model of Clostridium difficile infection.
“Mice received a strain of the RT027 lineage and a diet with or without low trehalose levels,” Dr. Collins said.
“What the mice ate made a difference to the virulence of the infection; mortality was higher in the group consuming trehalose.”
Further experiments showed that increased disease severity in the presence of trehalose could not be explained by the mice having higher numbers of bacteria, instead what made the disease more severe was that RT027 produced higher levels of toxins.
These and other experiments provide evidence that dietary trehalose has contributed to the predominance of epidemic Clostridium difficile lineages and to their virulence.
“An important contribution of this study is the realization that what we once considered a perfectly safe sugar for human consumption, can have unexpected consequences,” Dr. Collins said.
“Our results suggest that the effect of trehalose in the diet of patients in hospitals with RT027 and RT078 outbreaks should be further investigated.”
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J. Collins et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature, published online January 3, 2018; doi: 10.1038/nature25178
