New antibiotic packs a punch against bacterial resistance

May 29, 2017, The Scripps Research Institute
A colorized scanning electron micrograph of MRSA. Credit: National Institute of Allergy and Infectious Diseases

Scientists at The Scripps Research Institute (TSRI) have given new superpowers to a lifesaving antibiotic called vancomycin, an advance that could eliminate the threat of antibiotic-resistant infections for years to come. The researchers, led by Dale Boger, co-chair of TSRI's Department of Chemistry, discovered a way to structurally modify vancomycin to make an already-powerful version of the antibiotic even more potent.

"Doctors could use this modified form of without fear of resistance emerging," said Boger, whose team announced the finding today in the journal Proceedings of the National Academy of Sciences.

The original form of vancomycin is an ideal starting place for developing better . The antibiotic has been prescribed by doctors for 60 years, and bacteria are only now developing resistance to it. This suggests bacteria already have a hard time overcoming vancomycin's original "mechanism of action," which works by disrupting how bacteria form cell walls.

Boger called vancomycin "magical" for its proven strength against infections, and previous studies by Boger and his colleagues at TSRI had shown that it is possible to add two modifications to vancomycin to make it even more potent. "With these modifications, you need less of the drug to have the same effect," Boger said.

The new study shows that scientists can make a third modification—which interferes with a bacterium's cell wall in a new way—with promising results. Combined with the previous modifications, this alteration gives vancomycin a 1,000-fold increase in activity, meaning doctors would need to use less of the antibiotic to fight infection.

The discovery makes this version of vancomycin the first antibiotic to have three independent mechanisms of action. "This increases the durability of this antibiotic," said Boger. "Organisms just can't simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two."

Tested against Enterococci bacteria, the new version of vancomycin killed both vancomycin-resistant Enterococci and the original forms of Enterococci.

The next step in this research is to design a way to synthesize the modified vancomycin using fewer steps in the lab, as the current method takes 30 steps. But Boger calls this the "easy part" of the project, compared with the challenge of designing the molecule in the first place.

Even if the process isn't streamlined, Boger believes the new vancomycin's lifesaving powers make its production valuable. "Antibiotics are total cures for bacterial infections," said Boger. "Making this molecule is important, even by the current approach, if the failure of antibiotics continues."

Explore further: Scientists re-engineer antibiotic

More information: Akinori Okano el al., "Peripheral modifications of [Ψ[CH2NH]Tpg4]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics," PNAS (2017). www.pnas.org/cgi/doi/10.1073/pnas.1704125114

Related Stories

Scientists re-engineer antibiotic

February 9, 2006

Scientists have re-engineered an antibiotic that attacks bacteria by inhibiting cell wall synthesis, thereby significantly increasing its effectiveness.

Chemists modify antibiotic to vanquish resistant bacteria

September 17, 2014

Scientists at The Scripps Research Institute (TSRI) have devised a new antibiotic based on vancomycin that is powerfully effective against vancomycin-resistant strains of MRSA and other disease-causing bacteria.

Researchers find dangerous bacteria after sewer spills

July 20, 2016

University of South Florida researchers investigating the aftermath of a September, 2014 sewer line break in St. Petersburg, Florida, have found dangerous antibiotic-resistant bacteria in the untreated wastewater that gushed ...

Recommended for you

Wearable device measures cortisol in sweat

July 20, 2018

The hormone cortisol rises and falls naturally throughout the day and can spike in response to stress, but current methods for measuring cortisol levels require waiting several days for results from a lab. By the time a person ...

Researchers report two-faced Janus membrane applications

July 20, 2018

Named for the mythical god with two faces, Janus membranes—double-sided membranes that serve as gatekeepers between two substances—have emerged as a material with potential industrial uses. Creating two distinct "faces" ...

Chemists characterize the fatal fungus among us

July 19, 2018

Life-threatening fungal infections affect more than two million people worldwide. Effective antifungal medications are very limited. Until now, one of the major challenges is that the fungal cell wall is poorly understood, ...

Infrared sensor as new method for drug discovery

July 19, 2018

Using an infrared sensor, biophysicists at Ruhr-Universität Bochum (RUB) have succeeded in analysing quickly and easily which active agents affect the structure of proteins and how long that effect lasts. Thus, Prof Dr. ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

agamemnus
not rated yet May 30, 2017
Solithromycin has three mechanisms of action. Vancomycin would not be the first. See: "The solithromycin journey—It is all in the chemistry", and "In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains".

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.