Newly reconfigured antibiotic shows great promise against bacterial resistance
Al Saint Jacques, MDLinx | June 06, 2017
Researchers have reconfigured an existing antibiotic in such a way that could eliminate the threat of antibiotic-resistant infections for years to come. Scientists at The Scripps Research Institute (TSRI) in La Jolla, CA, led by Dale Boger, co-chair of TSRI’s Department of Chemistry, have discovered a way to structurally modify vancomycin to make an already-powerful version of the antibiotic even more potent, according to a study published in the journal Proceedings of the National Academy of Sciences.
Threat of antibiotic-resistant infections
The original form of vancomycin was an ideal starting place for developing better antibiotics, because the antibiotic has been prescribed by doctors for 60 years, and bacteria are only now developing resistance to it.
Threat of antibiotic-resistant infections
The original form of vancomycin was an ideal starting place for developing better antibiotics, because the antibiotic has been prescribed by doctors for 60 years, and bacteria are only now developing resistance to it.
The researchers noted that the original form of vancomycin was an ideal starting place for developing better antibiotics, because the antibiotic has been prescribed by doctors for 60 years, and bacteria are only now developing resistance to it. This suggests that bacteria already have a hard time overcoming vancomycin’s original “mechanism of action,” which works by disrupting the way that bacteria form cell walls.
Boger called vancomycin “magical” because of its proven strength against infections. In addition, previous studies by Boger and his TSRI colleagues had demonstrated 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 explained.
The new study demonstrates that scientists can make a third modification, which interferes with a bacterium’s cell wall in a new way, with promising results, they pointed out. Combined with the previous modifications, this alteration gives vancomycin a 1,000-fold increase in activity, meaning physicians would need to use less of the antibiotic to fight infection.
This 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.”
When the researchers tested the modified antibiotic against Enterococci bacteria, they found that the new version of vancomycin killed both vancomycin-resistant Enterococci and the original forms of Enterococci.
They pointed out that the next step in this research is to design a way to synthesize the modified vancomycin using fewer steps in the lab, because the current method takes 30 steps. But Boger characterizes this as 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,” stated Boger. “Making this molecule is important, even by the current approach, if the failure of antibiotics continues.”
In addition to Boger, the other authors of the study included first author Akinori Okano and Nicholas A. Isley, both of TSRI.
The study was supported by the National Institutes of Health (grants F32 GM114948 and CA041101).