C Difficile: Evolving Faster Than Science

But a ‘Serendipitous’ Finding Could Provide a Solution

Clostridium difficile is evolving into two separate species, and one group is highly adapted to spread in hospitals, according to researchers at the Wellcome Sanger Institute, London School of Hygiene & Tropical Medicine in England.

The researchers identified genetic changes in the newly emerging species that allow it to thrive on the Western sugar-rich diet, evade common hospital disinfectants, and spread easily. They estimate that this emerging species accounts for over two thirds of healthcare C. difficile infections. The results of their study could help inform patient diet and infection control in hospitals. 

C. difficile bacteria are the leading cause of antibiotic-associated diarrhea worldwide. Often found in hospital environments, C. difficile forms resistant spores that allow it to remain on surfaces and spread easily between people, making it a significant burden on the healthcare system.

To understand how the bacterium is evolving, researchers collected and cultured 906 strains of C. difficile isolated from humans, animals, and the environment. They found that this emerging species––C. difficile clade A–––accounted for approximately 70% of the samples from hospital patients. It had changes in genes that metabolize simple sugars, so the researchers then studied C. difficile in mice, and found that the newly emerging strains colonized the mice better when their diet was enriched with sugar. It had also evolved differences in the genes that are involved in forming spores, giving much greater resistance to common hospital disinfectants. These changes allow it to spread more easily in healthcare environments.

The CDC calls C. difficile a major health threat: It causes half a million infections and about 40 deaths a day in the United States. But researchers from the Monash Biomedicine Discovery Institute in Australia have discovered an antibiotic that could prevent life-threatening C. difficile-related diarrhea. The research, led by Professor Dena Lyras, was published in Nature Microbiology.

The researchers discovered—serendipitously—that a particular class of antibiotic, cephamycins, can prevent C. difficile spore formation. They were using a liquid commonly used to grow C. difficile in the laboratory and were puzzled that while the bacterium was able to grow, it was not able to produce spores. They found that there was a cephamycin in the media that prevented the formation of spores.

"To confirm this, we used assays to examine spore numbers and found that cultures containing cephamycins had a big reduction in spore numbers," lead author Dr. Yogitha Srikhanta said.

Treatment using cephamycins could significantly advance drug development to control other important spore-forming bacteria, the researchers say. "We looked at other pathogens including Bacillus cereus—a major contaminant in the food industry which causes food poisoning and spoilage, and showed that cephamycins can also reduce its spore production," Dr. Srikhanta said. The treatment strategy could also potentially counter diseases such as anthrax, caused by inhaling the airborne spores of Bacillus anthracis.

"Our preliminary study provides an entirely new route to treatment and controlling C. difficile infection,” said Srikhanta. “We can see there’s going to be a clinical use for the combination treatment we're pursuing."

Source: Monash University, August 13, 2019; Wellcome Sanger Institute, August 12, 2019