University School of Medicine in St. Louis have found a way to make
bacteria kill themselves instead of host cells.
Smith, Ph.D., study leader and a postdoctoral researcher at Washington
University School of Medicine, along with Thomas E. Ellenberger, DVM, Ph.D.,
the Raymond H. Wittcoff Professor and Head of the Department of Biochemistry
and Molecular Biophysics at the Washington University School of Medicine, and a
team of researchers, have developed a method of making bacteria use its own toxins on
itself rather than using it to kidnap or kill host cells.
use toxins to either kidnap or destroy host cells, but some are capable of
keeping the toxin inactive through the use of an antitoxin while carrying the
toxin themselves. This prevents self-destruction.
the Washington University School of Medicine researchers were able to do this
by examining the structures of the toxin and its antitoxin in Streptococcus
pyogenes, which is common infection-causing bacteria. The toxin
in Strep is known as Streptococcus pyogenes beta-NAD+
glycohydrolase, or SPN. The antitoxin is the immunity factor for SPN called
IFS. SPN's toxicity originates from its ability to use all of a cell's NAD+,
which is an essential part of "powering cell metabolism." IFS then
blocks SPN's admittance to NAD+ which protects the bacteria's energy
most important aspect of the structure is that it tells us a lot about how the
antitoxin blocks the toxin activity and spares the bacterium," said
knowledge led the team of researchers to find a way to make the antitoxin
inactive. They discovered that the antitoxin changes shape when it is not bound
to the toxin, which would allow the toxin to attack its own bacteria.
is the Achilles heel that we would like to exploit," said Ellenberger.
"A drug that would stabilize the inactive form of the immunity factor
would liberate the toxin in the bacteria."
are currently testing drugs that make it so the antitoxin is not bound to the
toxin, thus allowing the toxin to destroy the bacteria. To date, there are no
available drugs that target the bacteria's antitoxin molecules.
is a war going on between bacteria and their hosts," said Smith.
"Bacteria secrete toxins and we have ways to counterattack through our
immune systems and with the help of antibiotics. But, as bacteria develop
antibiotic resistance, we need to develop new generations of antibiotics."
This study was published in Structure.