Blocking Spore Formation in C. Diff with Cephamycins

In Australia, more than 10,000 patients a year acquire a serious bacterial infection called Clostridioides difficile, often while in the hospital, resulting in the deaths of up to 300 people. In the US, the bacterium causes around 40 deaths per day. The infection is often a result of antibiotics, which clear out much of the gut environment, allowing C. difficile to spread.

In a study published today in Nature Microbiology, Monash Biomedicine Discovery Institute researchers have discovered an antibiotic that could prevent the life-threatening diarrhea caused by C. difficile. The treatment strategy could also potentially counter diseases caused by other similar spore-producing bacteria, including the lethal anthrax, a key bioterrorism tool. The research was published today in Nature Microbiology.

“Infection with C. difficile arises because of the use of antibiotics,” says co–senior author Dena Lyras. “The increasing use of antibiotics has perpetuated the problem.”

The bacterium produces spores that lie dormant, allowing it to survive in environments where actively growing bacteria would normally perish. The spores can infect and re-infect patients, causing a disease that can last months.

The team serendipitously discovered that a particular class of antibiotic called cephamycins can prevent C. difficile spore formation. “To confirm this, we used assays to examine spore numbers and found that cultures containing cephamycins had a big reduction in spore numbers,” says first author Yogitha Srikhanta.

Treatment using cephamycins could significantly advance drug development to control other important spore-forming bacteria, the study found.

“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,” Srikhanta says. The authors believe that cephamycins could also potentially control anthrax, a disease caused by inhaling the airborne spores of Bacillus anthracis.

“What we’ve shown in our paper is that when we co-treat mice with the current best standard of care together with our treatment, we can prevent recurrent C. difficile disease,” says co–senior author Sheena McGowan. “That’s a big development because recurrent disease accounts for approximately one-third of C. difficile treatment costs worldwide.”