BOSTON (Sept. 5, 2007) As if being admitted to the hospital werent bad enough, patients, once admitted, are at higher risk of becoming infected with a superbug bacterium, Clostridium difficile (C. difficile). The toxins produced by C. difficile kill human intestinal cells by causing them to burst open, allowing the bacteria to use them as fuel. This results in severe diarrhea and, in rare cases, death. Abraham Linc Sonenshein, PhD, and colleagues from the Department of Molecular Biology and Microbiology at the Tufts University School of Medicine (TUSM) and the Sackler School of Graduate Biomedical Sciences at Tufts, have discovered how a protein called CodY regulates the genes that control production of the dangerous toxins. Understanding the relationship between CodY and C. difficile is an important step toward the development of a drug that may prevent hospital patients from falling ill.
The C. difficile bacteria only produce toxins when they are in need of food, explains Sonenshein, professor of microbiology at TUSM and corresponding author on the paper to be published in Molecular Microbiology. We found that the CodY protein, in essence, monitors the hunger level of C. difficile, preventing toxin production when the bacteria have enough to eat. Sonenshein, along with first author Sean Dineen, PhD, and other Tufts colleagues developed a series of experiments to investigate the importance of CodY and how this protein communicates to bacteria that it is time to search for new sources of food.
The researchers first developed a mutant strain of C. difficile bacteria that does not make the protein CodY, and compared the amount of toxin produced by the mutant strain of bacteria to the amount of toxin produced by normal bacteria. The mutant strain produced much higher levels of toxin. The presence of CodY seems to tell the bacterial cells that they are well-fed and there is no reason to make toxin that kills intestinal cells for fuel. Lack of Co
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Tufts University, Health Sciences