University of Arkansas, Fayetteville


Clostridium difficile infects millions of hospitalized patients worldwide, causing pseudomembranous colitis, a disease with symptoms attributable to two toxins produced by the bacterium.The PaLoc gene locus in the C. difficile genome is responsible for toxin production and activation, but it is not known how the toxins are released from the pathogen. Within PaLoc is a gene for the TcdE protein, which shares striking similarity to a class of membrane pore-forming proteins called holins. To assess whether TcdE catalyzes toxin release, the engineered tcdE gene was expressed in Escherichia coli. An arabinose promoter upstream of the tcdE gene was manipulated to modulate transcription of the gene. Recombinant E. coli cells showed viability and morphological changes, throughout different phases of growth, consistent with membrane pore formation. Thus, TcdE has the properties required of a toxin release mechanism, and drugs that block TcdE function could be candidates for drug therapy for treating infected patients.