Study: Genetic adaptations primed C diff for hospital transmission

Editor's note: This story was updated on Aug 14 with comments from Robert Britton, PhD.

A large genomic study of the gut bacterium Clostridioides difficile suggests the strains that have become endemic in healthcare systems around the world belong to an emerging species that's genetically adapted to spread among hospital patients.

The research, published in a letter yesterday in Nature Genetics, found that the emerging species of C difficile arose around 76,000 years ago and began to expand around the end of the 16th century, prior to the emergence of the modern healthcare system. Genomic analysis revealed that the ability of the strains in this species to spread in the healthcare system has been aided by genes that help them colonize the gut and produce hardier spores.

C difficile is the leading cause of hospital-acquired diarrhea in the world, but the explosion of cases and emergence of outbreak strains in hospitals has mainly occurred over the past 40 years, and has been linked to rising use of broad-spectrum antibiotics, which wipe out the normal gut bacteria that keep C difficile in check. When that balance is disrupted, C difficile multiplies and produces toxins that cause inflammation of the colon and severe diarrhea.

While antibiotics, and the acquisition of genes that make it more virulent and resistant to certain antibiotics, have played a significant role in making C difficile one of the most common healthcare-associated pathogens, these findings suggest that the genetic adaptations that have occurred over thousands of years set the stage for human, healthcare-related transmission.

Genomic analysis reveals an emerging species

To better understand how C difficile has evolved and what genetic changes have made certain strains more amenable to the healthcare environment, a team led by scientists from the Wellcome Sanger Institute performed whole-genome sequence analysis on 906 C difficile strains isolated from humans, animals, and environmental sources in 33 countries. More than half of the strains came from the United Kingdom, which saw major hospitals outbreaks of C difficile from 2003 to 2007. The collection of strains, which was designed to capture C difficile's genetic diversity, was categorized into four different phylogenetic groups: PG1, PG2, PG3, and PG4.

Analysis of the genetic differences among the strains found that PG1, PG2, and PG3 were all genetically closer to each other than to PG4 and lik