Teaching antibiotics to be more effective killers

December 12, 2017, University of Illinois at Chicago
Research shows prolonged inhibition of protein synthesis leads to cell death. Credit: Proceedings of the National Academy of Sciences

Research from the University of Illinois at Chicago suggests bond duration, not bond tightness, may be the most important differentiator between antibiotics that kill bacteria and antibiotics that only stop bacterial growth.

While both types of antibiotics are used to treat a variety of bacterial infections, – those that kill bacteria – can be taken for shorter periods, are associated with a lower risk of infection recurrence and often cure the infection much better than bacteriostatic antibiotics.

"Bacteriostatic antibiotics work by slowing the growth of bacterial cells while the individual's immune system fights the infection," said Alexander Mankin, lead author of the study and director of the Center for Biomolecular Sciences in the UIC College of Pharmacy. "Often, this is enough to treat an infection; but if the immune system is not strong enough, the may persist."

Unfortunately, not much is known about why the sometimes-similar antibiotic molecules interact differently with bacteria in the body.

Mankin and his colleagues looked at one class of antibiotics called macrolides, which work by binding to the of the bacteria to stop protein synthesis. However, while are all structurally similar and act on the same molecular target (the ribosome), some are bactericidal and others are bacteriostatic.

Using a new technique developed by Maxim Svetlov, a postdoctoral researcher in the lab of Mankin and Nora Vázquez-Laslop, an associate professor in the center, the researchers studied the differences between the bacteriostatic and bactericidal macrolides. The technique makes it possible to analyze how tightly the drugs interact with the ribosome and to measure the speed with which the antibiotics can disconnect from the target.

"Researchers usually think that it is the tightness of the drug's binding to the ribosome that makes the difference between an antibiotic that kills bacteria and one that only slows ," Mankin said. "Therefore, we were surprised to find that tightness of the drug binding does not define the ability of the drug to kill .

"Instead we understood that bactericidal drugs dissociate from the ribosome at a significantly slower rate," Mankin said.

The presence of an extended side chain in the structure of the antibiotic functions "like an extra hand to hold on to the ribosome; it allows the drug to bind for a longer period," says Mankin.

The findings, published in the Proceedings of the National Academy of Sciences, offer a new and previously unexplored possibility.

"The results of this study suggest that when we talk about the mechanism of antibiotic action, we need to talk about more than 'how tight' a drug binds," Mankin said. "We also need to talk about kinetics and the rate of a drug's disassociation from the ribosome."

In addition to improving outcomes for individuals who need , particularly for patients who are immunocompromised, understanding the difference between bacteriostatic and bactericidal may also help to address the problem of rising in society.

"If we can understand these mechanisms, we may be able to reduce the rate at which antibiotic resistance develops and repeat infections occur," Mankin said.

Explore further: Honeybees could play a role in developing new antibiotics

More information: Maxim S. Svetlov et al. Kinetics of drug–ribosome interactions defines the cidality of macrolide antibiotics, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1717168115

Related Stories

Two antibiotics fight bacteria differently than thought

November 1, 2016

Two widely prescribed antibiotics—chloramphenicol and linezolid—may fight bacteria in a different way from what scientists and doctors thought for years, University of Illinois at Chicago researchers have found. Instead ...

Scientists discover how some bacteria survive antibiotics

April 30, 2008

Researchers at the University of Illinois at Chicago have discovered how some bacteria can survive antibiotic treatment by turning on resistance mechanisms when exposed to the drugs. The findings, published in the April 24 ...

Recommended for you

Detecting metabolites at close range

June 22, 2018

A novel concept for a biosensor of the metabolite lactate combines an electron transporting polymer with lactate oxidase, which is the enzyme that specifically catalyzes the oxidation of lactate. Lactate is associated with ...

Research team uncovers lost images from the 19th century

June 22, 2018

Art curators will be able to recover images on daguerreotypes, the earliest form of photography that used silver plates, after a team of scientists led by Western University learned how to use light to see through degradation ...

CryoEM study captures opioid signaling in the act

June 22, 2018

Opioid drugs like morphine and fentanyl are a mainstay of modern pain medicine. But they also cause constipation, are highly addictive, and can lead to fatal respiratory failure if taken at too high a dose. Scientists have ...

Researchers achieve unprecedented control of polymer grids

June 21, 2018

Synthetic polymers are ubiquitous—nylon, polyester, Teflon and epoxy, to name just a few—and these polymers are all long, linear structures that tangle into imprecise structures. Chemists have long dreamed of making polymers ...

Template to create superatoms could make for better batteries

June 21, 2018

Virginia Commonwealth University researchers have discovered a novel strategy for creating superatoms—combinations of atoms that can mimic the properties of more than one group of elements of the periodic table. These superatoms ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.