Researchers worldwide are searching for ways to stay ahead of these rapidly changing microbes. One promising strategy is not to invent a completely new antibiotic, but to help existing drugs work again. This is the idea behind antibiotic adjuvants, which are companion molecules that do not kill bacteria directly but instead restore the power of antibiotics.

Building New Molecules to Speed Drug Discovery

Professor John Moses and his team at Cold Spring Harbor Laboratory (CSHL) have spent years developing chemical reactions that can make the drug discovery process faster and more efficient.

The researchers use a technique called diversity oriented clicking (DOC), which was created in the Moses laboratory. With this method, they have built a library containing more than 150 different compounds. Molecules from this collection have already contributed to research on both antibiotic resistance and cancer.

Now, through a collaboration with Scripps Research, the library has helped scientists restore the effectiveness of vancomycin. This powerful antibiotic is commonly used against severe infections, including those caused by MRSA and Clostridium difficile (C. diff). Both pathogens can develop resistance and become “superbugs” that evade frontline drugs such as vancomycin. They can then spread through hospitals, nursing homes, and communities.

Restoring Vancomycin Against Resistant Bacteria

In the new study, scientists from the Moses laboratory at CSHL worked with Professor Howard Hang’s team at Scripps to identify a way to make vancomycin effective again.

The researchers targeted a bacterial enzyme called secreted antigen A (SagA). They blocked the enzyme using a small molecule known as pghi-4, which was first discovered in the Moses laboratory in 2020.

When drug-resistant E. faecium was treated with both vancomycin and pghi-4, the antibiotic regained its ability to kill the bacteria.

For Moses, one of the most notable parts of the finding is that the research did not begin as a direct search for a new antibiotic.

“This discovery came from fundamental chemical research,” he explains. “Reaction development led to the discovery of the first inhibitor of an important enzyme involved in antibiotic resistance. This is a process we’re constantly refining to both keep our library of molecules up to date and add more for collaborators to take advantage of in their research.”

A Broader Strategy Against Superbugs

By making the molecular library available to other researchers, the team hopes similar approaches could eventually lead to treatments for additional drug-resistant infections. These could include resistant forms of tuberculosis.

“This work reflects a philosophy of chemistry that’s designed to accelerate drug discovery in its purest form,” says Moses. “By using reliable, robust, and intelligent chemical reactions, we can build new molecules more efficiently. That’s exactly the approach we used here.”

As antibiotic resistance grows around the world, the findings show that important medical advances may come from rethinking the chemistry of drugs that already exist. A future treatment may begin not with a new antibiotic, but with a carefully designed molecule that helps an old one work again.

Funding

National Institutes of Health, National Cancer Institute, Australian Research Council, New York State Biodefense Commercialization Fund, F.M. Kirby Foundation, Starr Foundation

The discovery offers the strongest evidence so far that planets with broadly Earth-like temperatures and rocky compositions may exist beyond our solar system while also retaining conditions that could potentially support life.

“An atmosphere is essential for a planet to support life as we know it,” said lead author Collin Cherubim, who recently earned his Ph.D. in Earth and Planetary Sciences from Harvard University.

“This is the first time anyone has found an atmosphere on a rocky planet in the habitable zone of another star.”

Helium Reveals an Exoplanet Atmosphere

The study, published July 16 in Science, describes observations of helium escaping from LHS 1140 b, a rocky exoplanet located about 48 light-years from Earth. The signal supports earlier theoretical predictions that the planet possesses an atmosphere.

LHS 1140 b circles a red dwarf star within its habitable zone. This is the region around a star where temperatures and other environmental conditions may allow liquid water to remain on a planet’s surface.

Scientists have identified thousands of exoplanets, including several rocky worlds in habitable zones. However, confirming whether those planets have atmospheres has been one of the most difficult challenges in exoplanet research.

“Twenty years ago we wondered whether other terrestrial-type planets even existed,” said Robin Wordsworth, Gordon McKay Professor of Environmental Science and Engineering and Professor of Earth and Planetary Sciences at Harvard and one of Cherubim’s dissertation advisors. “Then we learned they’re common, and found some in the habitable zone. The next question was whether any of them had managed to keep an atmosphere. Now we know at least one has.”

A Rocky World That Kept Its Atmosphere

Previous research has identified rocky planets orbiting within the habitable zones of their stars. This study, however, is the first to clearly show that one of those worlds has an atmosphere that may have endured for billions of years.

Cherubim and his colleagues developed a theoretical model predicting that the upper atmosphere of LHS 1140 b would contain large amounts of helium slowly escaping into space.

The researchers tested that prediction using the Warm Infrared Echelle (WINERED) Spectrograph at the Magellan Observatory in Chile. Their observations took advantage of an unusual event in which LHS 1140 b and another planet crossed in front of their star during the same night.

The second planet showed no sign of an atmosphere. LHS 1140 b, however, produced a clear signal of helium escaping from the planet, providing evidence that it still retains an atmosphere.

A Prediction Confirmed by Telescope Data

Cherubim’s joint advisor David Charbonneau, head of the Harvard Department of Astronomy and astronomer in the Center for Astrophysics | Harvard & Smithsonian, initially doubted whether the plan would succeed. The prediction came from a mathematical model, and this type of signal had never before been observed from a rocky world.

The results changed his mind.

“Collin analyzed the planets we knew about and predicted that this one would have a helium atmosphere,” Charbonneau said. “Then he organized telescope time, got the data, and the detection was statistically rock solid.”

The discovery indicates that astronomers may be able to study the atmospheres of rocky exoplanets from the ground by looking for gases escaping into space.

A Promising Target in the Search for Life

Astronomers estimate that the atmosphere of LHS 1140 b has survived for more than three billion years. That longevity makes the planet an especially promising target for additional observations.

Cherubim hopes to identify the atmosphere’s complete chemical composition and eventually determine whether the planet has surface oceans or other features connected with habitability. He and his colleagues also plan to use the model to search for additional rocky worlds with atmospheres.

“This has been a model validation, and hopefully it’s just the first of many more observations to come,” he said.