Did a Sugar Called Trehalose Contribute to the Clostridium difficile Epidemic?

https://goo.gl/m5QhhR

Scientists have recently discovered that a form of sugar called trehalose could be partly to blame for the rapid emergence around the turn of the millennium of certain epidemic-associated strains of the gut bacterium Clostridium difficile. The research, published in Nature and led by Baylor College of Medicine microbiologist Robert Britton, PhD, suggests that these strains have a unique ability to grow on low amounts of the sugar, which entered the North American and European food systems around the same time as C difficileoutbreaks in these regions.

The strains belong to 2 C difficile ribotypes, RT027 and RT078. Infections from C difficile had always caused diarrhea and colitis, sometimes leading to surgery and even death. But starting around 2000, as the previously rare ribotype RT027 spread, the infections became more common, more severe, more resistant to treatment, more likely to relapse, and more deadly.

Between 2001 and 2010, the US rate of C difficile hospitalizations per 1000 adult discharges roughly doubledfrom 5.6 to 11.5. In 2011, C difficile caused almost half a million infections and approximately 15 000 deaths. That year, RT027 was associated with around a third of health care–associated C difficile infections.

Antibiotic resistance alone doesn’t fully explain the trends. Although RT027 strains are resistant to fluoroquinolone antibiotics, so are other nonepidemic ribotypes. So what was giving this particular brand of C difficile its edge?

In 2014, Britton demonstrated that epidemic RT027 strains outcompete other nonepidemic C difficile strains in human fecal bioreactors and mouse models. But the mechanism behind their advantage was still unknown.

In their recent Nature study, funded by the National Institutes of Health, Britton and collaborators looked at how an epidemic strain of RT027 responds to around 200 food sources—sugars and sugar alcohols, amino acids, and proteins—found in the large intestine, where C difficile causes disease. One food source in particular—trehalose—stood out as increasing growth 5-fold compared with a non-RT027 strain.

The researchers then supplemented 21 strains from 9 C difficile ribotypes commonly found in the clinical setting with either glucose or trehalose alone. Most of the strains grew on low amounts of glucose, but only epidemic strains of RT027 and another outbreak-associated ribotype, RT078, grew on low amounts of trehalose.

“That was a smoking gun for us,” Britton said.