Researchers work to quell intestinal bacteria’s appetite

Even bacteria get really hungry. That’s the conclusion of Tufts researchers studying the genetics behind why Clostridium difficile causes disease. Simply put, the bugs create problems when they are ravenous.

The ubiquitous Clostridium difficile © CDC

“The genes responsible for toxin production only seem to be expressed during periods of nutrient deprivation. This is consistent with the view that most disease-causing bacteria express their pathogenicity when they are hungry,” Abraham Sonenshein, professor of microbiology, reported at the 107th general meeting of the American Society for Microbiology in May.

That finding might result in new treatments. According to the Centers for Disease Control, C. difficile causes tens of thousands of cases of diarrhea and at least 5,000 deaths in the United States each year. And the problem is getting worse. The number of C. difficile infections doubled between 1993 and 2003, with most of the increase coming after 2000.

C. difficile is a ubiquitous bacterium—found in soil, air, water, human and animal feces and on most surfaces in hospital wards. The bacteria don’t cause problems until they grow in abnormally large numbers in the intestinal tract. C. difficile-associated disease occurs when the normal intestinal flora is altered, often by the overuse of antibiotics. When the benign bacteria that normally reside in the intestines are reduced, then the gluttonous C. difficile can cause symptoms ranging from diarrhea to life-threatening inflammations of the colon.

A new, more virulent strain of C. difficile began showing up in hospitals in the United States and Canada in 2002, and Sonenshein’s research is attempting to quell the appetite of that deadlier strain.

He is studying a five-gene region of the bacterium’s chromosome known as the tcd locus. Two of the genes code for the disease-causing toxins the bacterium produces, and a third codes for a protein that makes a hole in the organism’s cell envelope to let the toxins out. Of greatest interest to Sonenshein and his colleague, Bruno Dupuy from the Institut Pasteur, are the gene that codes for a protein, known as R, which is necessary for the expression of three of the five genes, and another that codes for a protein, called C, which prevents R from acting.

A mutation in the C protein gene, which leaves R unchecked, is the cause of the new hyper-virulent strain. Sonenshein and his colleagues want to identify a protein that might shut down the gene that codes for R. By identifying such a protein, he hopes to find a way to change the appetite of the bacteria.

“If we find a way to shut down toxin production in the hyper-virulent strain, we might have a new way to treat the disease,” he said.

This story appeared in the July issue of the Tufts Journal.