Researchers seek weapon against new C. diff strain

Genetic code broken, seeding mild strains studied

An emerging highly virulent strain of Clostridium difficile is doing more than causing concern in the hospital — it’s spurring research in the lab.

Researchers are exploring novel approaches to defeat the pathogen, which has a genetic mutation that spurs increased toxin production, resulting in more severe infections and increased mortality.

Seeking to protect high-risk patients, one researcher is studying the possibility of colonizing them with nontoxic C. diff strains to thwart the emergence of the virulent variety. Patients become particularly vulnerable to C. diff after antibiotic use disrupts their normal enteric bacteria, which can be safely restored by seeding them with benign varieties of C. diff, says Dale Gerding, MD, associate chief of staff for research at the Hines VA Hospital and professor of medicine at Loyola University of Chicago. The research is promising, but currently is restricted to animal models using hamsters.

"These [C. diff] strains don’t make toxins or anything else that would harm people," he explains. "They were isolated from patients in hospitals and we have been putting them into hamsters to show that you can prevent disease from the very worst toxigenic strains that are out there. We are testing that model now against these new epidemic strains as well. You could target it at patients in the hospital that are receiving antibiotics, probably those that are elderly at most at risk for getting C. diff."

Meanwhile, researches at McGill University in Montreal have cracked the genetic code of the virulent C. diff strain. They have sequenced the genome of a virulent strain of C. diff that has been prevalent in Quebec since 2003. The sequencing of the genome may lead to detection, treatment, and prevention strategies for the deadly strain of C. diff.

"We are searching for other toxin and antibiotic resistance genes, and novel genome arrangements that will allow us to better understand why this strain causes severe disease," says Ken Dewar, MD, assistant professor of human genetics at McGill.