(Source: Craig L. Smith)
Making the protective antitoxin inactive allows the toxins to kill the bacteria

Researchers from Washington University School of Medicine in St. Louis have found a way to make bacteria kill themselves instead of host cells.  

Craig L. 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.

Bacteria 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.  

But now, 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 supply. 

"The 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 Ellenberger.

This 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.  

"This 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."

Researchers 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.  

"There 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.

"It looks like the iPhone 4 might be their Vista, and I'm okay with that." -- Microsoft COO Kevin Turner
Related Articles

Most Popular Articles

Copyright 2018 DailyTech LLC. - RSS Feed | Advertise | About Us | Ethics | FAQ | Terms, Conditions & Privacy Information | Kristopher Kubicki