How to turn bacteria against themselves

WASHINGTON - Researchers at Washington University School of Medicine in St. Louis have explained a mechanism by which bacteria protect themselves from their own toxins.

Bacteria often attack with toxins designed to hijack or even kill host cells. But they also have ways to avoid self-destruction.

The new study described one of these protective mechanisms, potentially paving the way for new classes of antibiotics that cause the bacteria’s toxins to turn on themselves.

Scientists determined the structures of a toxin and its antitoxin in Streptococcus pyogenes, common bacteria that cause infections ranging from strep throat to life-threatening conditions like rheumatic fever.

In Strep, the antitoxin is bound to the toxin in a way that keeps the toxin inactive.

“Strep has to express this antidote, so to speak. If there were no antitoxin, the bacteria would kill itself,” said Craig L. Smith, first author of the study.

With that in mind, Smith and colleagues may have found a way to make the antitoxin inactive. They discovered that when the antitoxin is not bound, it changes shape.

“That’s the Achilles’ heel that we would like to exploit. A drug that would stabilize the inactive form of the immunity factor would liberate the toxin in the bacteria,” said Thomas E. Ellenberger, another author.

In this case, the toxin is known as Streptococcus pyogenes beta-NAD+ glycohydrolase, or SPN.

With the structures determined, researchers can now test possible drugs that might force the antitoxin to remain unbound to the toxin, thereby leaving the toxin free to attack its own bacteria.

The research paper appeared Feb. 9 in the journal Structure. (ANI)