A CRISPR-based system that spreads through bacterial populations like a gene drive could offer a new way to tackle antibiotic resistance, one of the most urgent threats in modern medicine. Researchers at the University of California San Diego have developed a tool that does not simply kill resistant bacteria, but instead removes the genes that make them drug-resistant – potentially restoring the power of existing antibiotics.

The strategy builds on an earlier platform called Pro-Active Genetics, or Pro-AG, which uses CRISPR to target resistance genes carried on plasmids, the mobile DNA circles that bacteria readily share with one another. The new version, pPro-MobV, adds a conjugation-based transfer system, allowing the anti-resistance cassette to move efficiently from one bacterial cell to the next through a natural “mating” process. 

As co-author Ethan Bier explained (in a press release), “with this new CRISPR-based technology we can take a few cells and let them go to neutralize AR in a large target population.” Once transferred, the system disrupts antibiotic resistance genes and spreads that edit through the population. In laboratory experiments, the researchers showed that it could reduce antibiotic-resistant bacteria by as much as three to five orders of magnitude.

Importantly, the system also worked in biofilms – dense, surface-bound bacterial communities that are notoriously difficult to eliminate and are implicated in many chronic infections. “The biofilm context for combating antibiotic resistance is particularly important,” Bier noted, highlighting one of the biggest challenges in clinical and environmental settings. 

Because biofilms can form in hospitals, aquaculture systems, and wastewater facilities, the findings suggest applications well beyond the lab. The team also built in a safeguard mechanism, called homology-based deletion, that can remove the inserted genetic cassette if necessary. With the added possibility of delivering components by bacteriophages as well as plasmids, the platform could eventually be adapted for clinical, environmental, or industrial use – pointing to a future where resistant bacteria are disarmed rather than simply destroyed.