A group of scientists in the United States has developed a strong antibiotic against superbugs by re-engineering a decades-old antibiotic. The findings were published Monday in the journal Proceedings of the National Academy of Sciences.

The spread of antibiotic-resistant superbugs has risen significantly across the world, threatening to return medicine to the pre-antibiotic era, as deadly infectious diseases keep making a comeback. The Centers for Disease Control and Prevention estimate that more than 2 million people in the U.S. get antibiotic-resistant infections, and they noted that at least 23,000 of them die each year. Unless stronger antibiotics are developed, the toll will keep rising. However, scientists at The Scripps Research Institute in La Jolla, believe they have developed such antibiotic.

A researchers at the Walter Reed Army Institute of Research tests the mcr-1 superbug. Image credit: Walter Reed Army Institute of Research.

New vancomycin is more than 1,000 times as potent as the old version

The scientists developed a new form of vancomycin, an antibiotic that has been available for years. The team, led by Dale Boger, co-chair of TSRI’s Department of Chemistry, introduced three new modifications to vancomycin, the three lethal to bacteria and independent from each other. Superbugs would need to overcome all three changes to survive, but the scientists believe it is extremely unlikely.

Boger and his colleagues believe their study does not solve the problem of antibiotic-resistant superbugs, but it may slow down the process. They believe the solution is better science, to engineer antibiotics to anticipate and create resistance from the start.

The newly modified vancomycin still needs further development until it’s ready to be tested in people, to prove its efficacy and safety. Moreover, the scientists developed the drug through a lengthy 30-step process, and they are working on shortening the process.

The study said that even with the current synthesis method, the vancomycin should be medicinally useful. The researchers noted it’s more than ten times as potent as an earlier version that had two lethal modifications. With the third lethal modification, the new vancomycin is more than 1,000 times as potent as standard vancomycin itself.

Vancomycin ‘vacuums’ an essential oligopeptide that bacteria needs to function

Experts have already praised Boger and his team’s work, calling it a chemical synthesis of the highest order. Derek Lowe, a medicinal chemist, said he’s excited about the report and looks forward to seeing what the new form of vancomycin will be when it’s further developed. In a 2015 post on his blog, Lowe praised a previous investigation on the research that introduced the two lethal modifications.

Boger’s previous study on vancomycin, according to Lowe, is the kind of feat that requires intense human creativity. He believes the new investigation shows even more chemical tricks.

In recent years, fear of losing antibiotics has made doctors restrict their use.  Image Credit: KVUE

“Vancomycin’s original odd mechanism of action is why it’s lasted so long in the first place,” said Lowe in an email to The San Diego Union-Tribune. “It doesn’t bind directly to a bacterial protein, which would engage the evolutionary battle directly, but instead vacuums up a key oligopeptide that the bacteria need to function.”

Lowe explained that throwing these new functions on top of that results in not only getting a big boost in potency, but it also makes it far less likely that a bacterium will emerge that will be able to deal with everything at once.

He suggested that although the study is quite promising, it must be followed up with studies in animals. Lowe said he expects the new vancomycin to work on animals, but it has to be proven, as it may need to be “tweaked” in other ways for improved activity in a whole organism.

Dan Kahne, a professor of chemistry at Harvard University, described Boger’s work as “spectacular.” According to Kahne, engineering a molecule of the complexity of vancomycin is a feat that few synthetic groups in the world could even attempt. He added that they all need to continue to support these kinds of research programs because resistance will develop to any antibiotic.

Superbugs thrive in natural selection, and they’ve been around for millions of years

Bacteria exist in large numbers, they often mutate and swap genes with others, even between species. So when bacteria is confronted with antibiotics, it rapidly spreads. Vancomycin helped to stop this evolution for decades because it indirectly attacks bacteria by removing the oligopeptide. However, some bacteria proves to be resistant even if it’s attacked by vancomycin.

The process has spurred the increase of vancomycin-resistant enterococci, or VRE, which are bacterial strains that spread relentlessly. Enterococci are a group of bacteria known for their resistance, as their origin was traced back to at least 425 to 450 million years ago. As VRE have survived catastrophes for millions of years, it’s safe to say the emergence of VRE and other resistant organisms appears inevitable. Given that, doctors have become more cautious when prescribing antibiotics, hoping to reduce the pressures of natural selection that fuel resistance.

The researchers stated that restricting antibiotic use doesn’t do anything to generate an understanding of how resistance arises and how it might be thwarted. The modified vancomycin provides a positive answer, said the researchers, not only by itself but as an approach to developing other more durable antibiotics. Image credit: Washington Post

“Although sounding attractive, the effort to restrict antibiotic use seems counter to their importance, introduces guilt even their most legitimate of uses, challenges the prevailing practices of initial empirical best guess therapy and prophylaxis deployment, and produces additional disincentives to antibiotic development,” the study reads.

Source: San Diego Union-Tribune