Two specific lineages of Clostridium difficile rose from the biological stew to become the dominant hospital-acquired infections in the developed world in the 21st century.

A new study in the journal Nature contends that the rise of the deadly strains RT027 and RT078 was fueled by a food preservative which was approved in the year 2000.

The food additive is trehalose, an additive used in a wide variety of foods from produce to processed sweets, and even seafood. 

“We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence,” conclude the scientists, led by a quartet from the Baylor College of Medicine in Houston.

The doctors first experimented with what sustenance the two strains preferred. They discovered that trehalose can served as a single source of carbon – and the germs can grow in low levels of the molecule. (The RT027 and RT078 strains require 1,000 times less of the stuff than their C. diff competitors, they found).

Follow-up genetic sequencing found a single-nucleotide variant, which causes a protein change that allows the two lineages to metabolize low levels of the trehalose.

They then tested the strains in mice, with a varying diet of the sugar. The mice with more trehalose suffered worse, and died more, they report. The results also showed that the strains produced more toxins – explaining the increase virulence, they add.

“In 2000, trehalose was approved as a food additive in the United States for a number of foods from sushi and vegetables to ice cream, about three years later the reports of outbreaks with these lineages started to increase,” said Robert Britton, a Baylor microbiologist and co-author of the work. “Other factors may contribute, but we think that trehalose is a key trigger.

The germs existed for decades before their rise to deadly prominence, they add.

“These lineages have been present in people for years without causing major outbreaks,” said James Collins, first author, postdoctoral associate at Baylor. “In the 1980s they were not epidemic or hypervirulent but after the years 2000 they began to predominate and cause major outbreaks. We wanted to know what had helped these lineages become a major health risk.

“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,” said Collins.