Green Light Activates This Antibiotic Only Where It’s Needed

Researchers have modified penicillin to be activated only when exposed to green light, offering a more efficient and targeted approach to treating bacterial infections.

The innovative method could reduce the environmental impact of antibiotics by preventing the release of excess active medicines into wastewater, a known contributor to antimicrobial resistance.

The research is published in ACS Central Science.

How the green light activation works

To ensure precise control over antibiotic activity, the research team added a light-sensitive molecule to penicillin that reacts exclusively to green light. This modification keeps the antibiotic inactive in the body until green light is applied. Upon exposure to green light, the added molecule breaks away, activating the drug. This approach offers more targeted treatment, as the antibiotic is only active in the desired location.

Previous light-reactive tags, such as coumarin added to the opioid reversal agent naloxone, have required high-energy UV light or blue light to kick-start the process. Unlike those previous compounds, this new approach makes use of coumarin compounds that can be released by green light, which is a more "gentle" option for antibiotic activation.

“Controlling drug activity with light will allow precise and safe treatment of localized infections,” said Wiktor Szymanski, corresponding author of the study. “Moreover, the fact that light comes in different colors gives us the ability to take the spatial control of drug activity to the next level.”

Testing the system in bacteria and insects

In laboratory tests, the researchers modified penicillin by linking a coumarin-based molecule to the part of the drug that targets bacterial cell walls, rendering it inactive. As predicted, the molecule detached following green light exposure, allowing the penicillin to inhibit the growth of bacteria.

In petri dish experiments, the modified penicillin effectively inhibited the growth of Escherichia coli and the formation of Staphylococcus epidermidis biofilms.

The researchers also tested the modified antibiotic in living organisms by treating wax moth larvae infected with Staphylococcus aureus, a bacterium that causes human infections. Larvae that received an injection of the light-activated penicillin followed by green light therapy had an improved survival rate of 60%, significantly higher than the 30% survival rate of untreated larvae.

Future directions for light-activated antibiotics

These promising results suggest that green light-activated antibiotics could be developed further for other applications, such as use in humans. The researchers envision expanding this method to incorporate multiple light sources or different colors of light, providing even more enhanced control over the antibiotic’s activity.

Reference: Schulte AM, Schoenmakers JWA, van Oosten M, et al. Green-light-activatable penicillin for light-dependent spatial control of bacterial growth, biofilm formation, and in vivo infection treatment. ACS Cent Sci. 2025. doi: 10.1021/acscentsci.5c00437

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