Study Sheds Light on Clostridium Difficile’s Ability to Infect People
New research identifies key system in C. difficile that regulates the pathogen’s virulence
Washington, D.C. - December 22, 2020 – A new study has shown that 2 genes within Clostridium difficile, AgrB1 and AgrD1, are involved in multiple functions, including the ability of the organism to form spores, move and produce toxin. The study, , an open-access journal of the American Society for °®¶¹´«Ã½, provides clues as to how researchers could manipulate C. difficile and its ability to infect people.
“From a very basic bacteriology standpoint, it’s somewhat of a novel discovery that this system is involved in so many different events at one time,” said Jimmy Ballard, PhD, professor and chairman of the Department of °®¶¹´«Ã½ and Immunology, the University of Oklahoma Health Sciences Center, Oklahoma City, and principal investigator of the study. “Agr can be targeted with drugs and other methods to inhibit its activity and prevent the organism from making toxins or sporulating, so we think it is a good target for developing therapeutics.”
C. difficile is a spore-forming, toxigenic, anaerobic bacterium that produces toxins in the intestinal tract and causes antibody-associated diarrhea in the gut, which can be severe. It is also a member of a group of bacteria that forms environmentally resistant spores that can survive outside the host for a long time, which is one of the ways that this organism is acquired in the hospital.
Using the CRISPR gene editing system, the researchers performed several experiments while deleting AgrB1 and AgrD1. “We asked some fundamental questions about how the Agr system functions, how it influences sporulation, motility and the ability of the organism to produce toxin,” said Dr. Ballard.
The researchers found that deletion of AgrB1, AgrD1 or the entire locus resulted in changes in transcription of sporulation-related factors and an overall loss in spore formation. “We found that in some instances, both genes are necessary for sporulation,” said Dr. Ballard. C. difficile motility was reduced only when both AgrB1 and AgrD1 were disrupted. While deletion of AgrB1 caused it to create more toxin, the combined deletion of AgrB1/AgrD1 or deletion of only AgrD1 did not significantly effect toxin expression. “This finding suggests that the path can connect with other things that are necessary to regulate toxin production. There are things that we don’t understand about the entire system,” said Dr. Ballard.
Dr. Ballard said that understanding the ways in which C. difficile senses growth conditions to regulate toxin expression and sporulation is essential to advancing the understanding of this pathogen. “The key finding of this paper is the identification of the Agr system as a major regulator of multiple events important for the virulence of this pathogen,” said Dr. Ballard. If researchers can find a way to manipulate the Agr system to alter spore formulation, they could potentially impact the ability of the bacteria to infect people and stop transmission of C. difficile in hospitals.
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