backtop


Print 17 comment(s) - last by mmatis.. on Feb 9 at 6:37 PM


  (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.



Comments     Threshold


This article is over a month old, voting and posting comments is disabled

RE: eh, not quite yet...
By geddarkstorm on 2/9/2011 2:34:56 PM , Rating: 2
Actually, the hurdle isn't in finding a compound that'll stabilize the inactive form of the toxin, that'll be a sinch using molecular docking simulations. Such things are done routinely and effectively for a myriad of proteins, especially associated with human diseases; it is the foundation of modern drug development. It's where a large amount of the drugs on the market come from, when coupled with "shot-gun" screening methods of large chemical libraries against the target.

No no, the hurdle won't be in finding a compound that can inactivate the antitoxin and kill the bacteria. The hurdle will be in making sure it's safe in us, that it can get to the bacteria when its in us, that it can enter the bacteria and reach the site of action, and that the killing of the bacteria won't unleash a sudden mass blast of toxin into the human body to disastrous effect (think what Anthrax does, except it's causing the white blood cells to detonate and flood the body with self toxins). Also, will this only work for a particular strain or species of bacteria? Will there be wide spectrum versions producible? Just how unique are these antitoxins and are there backup variations in the bacteria that would nullify and complicate drug production?

So really, those "two hurdles" you list are the LEAST of the hurdles. Don't expect seeing drugs that exploit this for at least 5 years. But if effective, this could be particularly powerful.


"Spreading the rumors, it's very easy because the people who write about Apple want that story, and you can claim its credible because you spoke to someone at Apple." -- Investment guru Jim Cramer

Related Articles













botimage
Copyright 2014 DailyTech LLC. - RSS Feed | Advertise | About Us | Ethics | FAQ | Terms, Conditions & Privacy Information | Kristopher Kubicki