Scientists hope a new discovery will give a boost to vancomycin, a “last resort” antibiotic that’s effectiveness has been weakened by bacteria resistant to its actions.
First introduced in 1958, vancomycin is used to treat infections when other antibiotics fail. However, starting in the late 1980s, vancomycin-resistant bacteria emerged, leading scientists to engineer more powerful versions of the drug.
Now, researchers have developed a new version of vancomycin that may prove to be even more successful than previous versions.
The upgraded compound attacks bacteria in three different ways, which have proven to be thousands of times more powerful than the original version, according to lab test results.
Long quest for improved vancomycin
Vancomycin kills by preventing bacteria from building cell walls. It does this by binding to cell wall precursors, which contain two copies of the amino acid D-alanine.
Bacteria that are resistant to vancomycin have replaced one D-alanine with another amino acid, D-lactic acid. This change from the double D-alanine reduces vancomycin’s ability to bind to its target by 1,000 fold. As a result, it’s less effective at killing bacteria.
Bacterial infections can be deadly. More than 23,000 people die each year from infections caused by organisms resistant to antibiotics or antimicrobial drugs, according to the Centers for Disease Control and Prevention (CDC).
Around 1,300 of these deaths are due to vancomycin-resistant Enterococcus — bacteria that have been labeled a “serious threat” by the CDC.
Vancomycin-resistant Staphylococcus aureus (VRSA) — which causes staph infections — also exists, but is less common.
In 2011, researchers at The Scripps Research Institute in La Jolla, Calif., redesigned vancomycin so that it could bind to the cell wall precursor that contains both D-alanine and D-lactic acid, a so-called “pocket” modification.
“Many view this as important, beautiful work because it involves a change to a single atom in vancomycin to counter a single atom change in the bacterial cell wall precursor,” study author Dale Boger, PhD, co-chair of The Scripps Research Institute’s Department of Chemistry, told Healthline.
But there’s more to the story. Not only did the redesigned vancomycin bind to bacteria that had one D-alanine and one D-lactic acid. It was also able to bind to the bacteria with the double D-alanine in their cell wall precursors.
So this new version of vancomycin was effective against both resistant and nonresistant bacteria.
However, the researchers didn’t stop there.
Three-mode antibiotic more potent
In a new study published May 23 in the journal Proceedings of the National Academy of Sciences, Boger and his colleagues describe how they “set out to improve” vancomycin even further.
Adding on to their 2011 modification, they added two new mechanisms of action to “pocket-modified” vancomycin in an effort to further undermine resistant bacteria.
One peripheral modification blocks bacteria from synthesizing cell walls. The other causes the bacterial membrane to leak, which leads to cell death.
This approach greatly enhanced vancomycin’s antimicrobial abilities.
“The peripheral modifications improve potency activity — and in the end durability — not by enhancing primary target binding, but by acting by independent mechanisms of action,” said Boger.
Researchers tested the compound in the lab. It was 25,000 to 50,000 times more potent than the original form of vancomycin against vancomycin-resistant Enterococcus.
It was also 250 to 500 times more potent than the type of vancomycin currently used in clinics.
In addition, when researchers tested vancomycin-resistant Enterococcus against the three-part compound, the bacteria were unable to develop resistance even after 50 rounds.
Many antibiotics fail after a few rounds.
This may mean that the compound will be more durable — lasting a long time before the bacteria fight back and become resistant to the medication.
“An antibiotic to which bacteria cannot develop resistance is the Holy Grail,” David Weiss, PhD, associate professor of medicine, and director of the Emory Antibiotic Resistance Center at Emory University, told Healthline.
“It seems unlikely this is possible,” he added, “but we can certainly develop antibiotics to which resistance is much less likely to occur, and the present study does a beautiful job of that.”
Weiss was not involved in the latest study.
Boger thinks the new compound would be durable because if bacteria succeeded in overcoming one of the antibiotic’s mechanisms of action, they would still be killed by the other two. In order to develop resistance, bacteria would need to overcome all three mechanisms of action at the same time — an unlikely, but not impossible, scenario.
“Bacteria have so many different ways to resist antibiotics, it seems impossible that resistance will not eventually develop,” said Weiss. “For example, even if the [bacterial] cells cannot withstand the action of the modified vancomycin, they could find a way to sequester it or degrade it and thus preemptively avoid its activity.”
The new compound still has a long way to go before it can be used in the clinic, including animal tests and human clinical trials. Only then will scientists know if it is safe and effective.
“It will be important to test this new modified antibiotic in the setting of an infection in the future,” said Weiss. And he added that not everything that works in the lab ends up working in real-life situations.
Boger said he also hopes to simplify production of the compound — currently it takes 30 steps. This would make it cheaper and more useful as another line of defense against dangerous infections.
Weiss said that most approvals for new antibiotics over the past few decades have been for “derivatives of existing classes,” like the work done by Boger’s group.
But it’s not the only method of protecting people from infections.
“There is now an increased focus on identifying new classes [of antibiotics],” said Weiss. “Given the crisis that we face, all approaches are necessary and welcome.”
Even if the new vancomycin succeeds in the clinic, scientists probably won’t be able to rest anytime soon, especially when working against the adaptability of the microscopic world.
“Scientists are, and will always be, trying to stay one step ahead of bacterial evolution,” said Weiss.