C. difficile evolution

Scientists find that C. difficile is evolving into two separate species—and the emerging species is adapted to spreading through hospital environments

Kelsey Kaustinen
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CAMBRIDGE, Mass.—Hospital-acquired infections are a leading—and rising—issue in hospital environments. Not only do they threaten the health and recovery of individuals whose immune systems are likely already stressed, the contained environment and widespread use of antibiotics can be a breeding ground for antibiotic-resistant bacteria. One such common strain is Clostridium difficile, and some of the latest research into this bacteria has discovered that it is evolving into two separate species—one of which is tailor-made for spreading in hospitals. The research was published this week in Nature Genetics by a team of researchers from the Wellcome Sanger Institute, London School of Hygiene & Tropical Medicine, and other collaborators, in a paper titled "Adaptation of host transmission cycle during Clostridium difficile speciation."
 
This study was the largest genomic study of C. difficile to date. As noted in the abstract, the researchers applied genomic analysis to 906 strains of C. difficile, which were isolated from humans, animals (such as dogs, pigs and horses), and the environment.
 
“This largest ever collection and analysis of C. difficile whole genomes, from 33 countries worldwide, gives us a whole new understanding of bacterial evolution. It reveals the importance of genomic surveillance of bacteria. Ultimately, this could help understand how other dangerous pathogens evolve by adapting to changes in human lifestyles and healthcare regimes which could then inform healthcare policies,” said Prof. Brendan Wren of the London School of Hygiene & Tropical Medicine, one of the authors of the Nature Genetics paper.
 
The emerging species, known as C. difficile Clade A, was found to have first appeared roughly 76,000 years ago, according to dating analysis. However, the number of strains of this species began rising at the end of the 16th century, before modern hospitals became a feature of society. In their study, this species of C. difficile was found to comprise roughly 70 percent of the samples from tested patients.
 
The specifics that make C. difficile Clade A problematic are certain genetic changes. This species has evolved to better metabolize simple sugars, which is likely a response to the high sugar content of the typical Western diet. When tested in mice, the new strains of Clade A better colonized the mice when their diet had a higher sugar content. In addition, this strain of C. difficile presents with differences in the genes that form its spores, which grant it greater resistance in the face of typical hospital disinfectants, according to a Wellcome Sanger press release.
 
“Our study provides genome- and laboratory-based evidence that human lifestyles can drive bacteria to form new species so they can spread more effectively. We show that strains of C. difficile bacteria have continued to evolve in response to modern diets and healthcare systems and reveal that focusing on diet and looking for new disinfectants could help in the fight against this bacteria,” remarked Dr. Trevor Lawley, the senior author from the Wellcome Sanger Institute.
 
C. difficile infection results in diarrhea and colitis (inflammation of the colon), and causes nearly 500,000 illnesses in the United States alone every year, according to the U.S. Centers for Disease Control and Prevention. Of those patients who contract C. difficile, one in five will get it again. The CDC also notes that within just a month of being diagnosed, one in 11 people over the age of 65 have died from a healthcare-associated C. difficile infection. As noted in a Wellcome Sanger Institute press release, “good” bacteria normally keep C. difficile in check in the gut of healthy individuals. When taking antibiotics, however, such as in a hospital setting, “good” bacteria can get eliminated along with bad bacteria, which increases the risk of C. difficile infection.

Kelsey Kaustinen

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