Clostridium difficile is Starving!
Researchers have often wondered why bacteria suddenly become virulent after laying dormant for long periods. Maybe now they have the answer?
TORONTO – May 24, 2007 -- Researchers studying the genetics
behind why C. difficile causes disease have come to a simple conclusion
-- the bacteria do it because they are starving. That just might help them
find a new treatment for what can sometimes be a very difficult disease
“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,” says Abraham Sonenshein, professor at the
Sackler School of Graduate Biomedical Sciences at Tufts University and
at Tufts University School of Medicine, at the 107th General Meeting of
the American Society for Microbiology (ASM) on May 24, 2007.
C. difficile bacteria are everywhere — 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. This can happen when the benign bacteria that normally
inhabit the intestinal tract are reduced such as when people take
antibiotics or other antimicrobial drugs. Then, C. difficile can cause
symptoms ranging from diarrhea to life-threatening inflammations of the
In 2002 a new, more virulent strain began appearing in hospitals in
the United States and Canada. Recently, this strain was shown to be
responsible for more than half of all cases in a representative sampling in
Quebec. The highly virulent strain has a much higher toxin production
which leads to more destructive and deadly disease, says Vivian Loo of
Sonenshein is studying a five-gene region of the bacterium’s
chromosome known as the tcd locus. Two of the genes code for the
toxins the bacterium produces that cause disease and a third gene
codes for a protein that makes a hole in the organism’s cell envelope to
let the toxins out. The last two genes are of greatest interest to
Sonenshein and his colleague, Bruno Dupuy from the Institut Pasteur.
One codes for a protein, known as R, that is necessary for the
expression of the first three genes and the other codes for a protein
called C that prevents R from acting.
A mutation in the C protein gene, leaving R unchecked, is the cause
of the hypervirulent strain. Sonenshein and his colleagues are currently
working to identify a protein that might shut down the gene that codes
for R. By identifying such a protein, Sonenshein hope to find a way to
change the appetite of the bacteria. “If we find a way to shut down toxin
production in the hypervirulent strain, we might have a new way to treat
the disease,” says Sonenshein.
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