Since the discovery of penicillin in 1928, scientists have been running a never-ending race against evolution. Every time patients are treated with antibiotics and antifungals for infections from strep throat to athlete’s foot, the bacteria are exposed to new selective pressures. They, like any life form following Darwinian evolutionary patterns, must adapt to survive — and they do so by developing antibiotic resistance.

Each year in the United States, more than 2.8 million antimicrobial-resistant infections occur, leading to at least 35,000 deaths. At least 700,000 people die each year because their diseases cannot be treated with antibiotics. This means new antibiotics must be discovered, isolated, developed, tested, and mass-produced — and the race against evolution continues.

Germs — which are microscopic organisms like fungi, bacteria, and protozoa — are found everywhere in our bodies, but some cause more harm than help. Antibiotics are medications administered to kill these germs. Penicillin, for example, destroys bacteria by rupturing their cell walls. However, bacteria can evolve to become resistant to penicillin by acquiring an antibacterial resistance (AR) gene from a resistant neighbor. This is a process called horizontal gene transfer, when genes are not passed down through generations like in humans, but instead are picked up from other bacteria that have survived nonlethal doses of antibiotics.

Once the antibacterial resistance gene, encoded on a small DNA molecule called a plasmid, is picked up, it can easily be integrated into the bacteria’s genome. However, two professors at the University of California San Diego, Ethan Bier and Justin Meyer, have found a way to harness gene-editing technology to neutralize these plasmids.

The saga started seven years ago, in 2019, when Bier and his team created a tool called Pro-Active Genetics (Pro-AG), which allowed them to genetically inactivate the AR genes within individual bacterial cells using CRISPR Cas-9.

CRISPR Cas-9 is a gene editing tool found in bacterial immune systems. It uses the Cas9 protein as molecular scissors, guided by a template sequence to create a double-strand break in DNA at a specific genetic locus. The natural repair mechanisms of the cell then stick the broken ends of DNA back together, often disrupting or deleting the target gene sequence.

Bier’s Pro-AG tool used CRISPR-Cas9 to successfully cut the target AR gene, and inserted a new sequence that inactivated all copies of the AR gene throughout the bacteria’s genome. Unfortunately, this strategy was clunky. Pro-AG involved three separate plasmids to encode the CRISPR-Cas9 machinery, and there was no way to make bacteria spread these specific plasmids using horizontal gene transfer. A new delivery method was needed.

In 2023, scientists at the University of Exeter engineered a single plasmid-based delivery vehicle that delivered a CRISPR Cas-9 complex designed to target AR sequences in the bacterial genome of E. coli. Like Pro-AG, this plasmid not only cut pre-existing AR genes, but could also block future uptake of AR plasmids via insertion of a short DNA sequence. This plasmid was then easily copied between bacteria using horizontal gene transfer, which inactivated their AR genes.

In essence, scientists turned the bacteria’s own gene-sharing ability against it. By enabling the spread of an engineered plasmid between bacteria, Bier and his team could take advantage of the way bacteria often coagulate in biofilms, where they use the power of teamwork to resist antibiotics.

Biofilms can grow on a wide range of media, from medical devices like catheters and heart valves to sewage treatment plants to hot springs. While these communities of microorganisms contribute in their own way to our ecosystem, it’s not in our best interest to host them inside our bodies. Biofilm-based infections can evade the immune response and have higher immunity to antibiotics, often associated with chronic infections like cystic fibrosis.

Bier wanted to find a way to take advantage of the way bacteria within biofilms can pass around AR genes in order to distribute Pro-AG. He was joined by Meyer, an evolutionary microbiologist, to combine their Pro-AG methodology with the CRISPR-Cas9 plasmid, which could theoretically penetrate these dense microbial communities. In early 2026, the pair revealed that they had engineered Pro-AG into a single plasmid that contained everything necessary for its dissemination into AR-positive bacteria, naming it pPro–MobV. Bier claims that due to the effectiveness of large-scale administration of pPro-MobV, scientists are able to “take a few cells and let them go to neutralize AR in a large target population."

However, there are still concerns about pPro-MobV’s level of regulation. If horizontal gene transfer spins out of control, it poses risks of disrupting microbial ecosystems and unintended consequences in environmental bacteria. Self-spreading genetic tools like this one always raise some level of concern, which is why long-term monitoring would be necessary.

On the bright side, the creation of a self-propagating AR inactivation system could quell fears about ‘superbugs’ rendering current antibiotics useless. Meyer claims their technology is able to “actively reduce the spread of antibiotic-resistant genes.” It could lower the rate of hospital-acquired infections, and help protect certain strains of wheat. Bier and Meyer’s pPro-MobV requires further monitoring, but if successful, would be a huge boon in the century-long race against antibiotic resistance.