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“Living medicine” recruits bacteria to fight antibiotic-resistant superbugs

Scientists have demonstrated a new way to fight antibiotic-resistant superbugs by pitting bacteria against each other. The team engineered a common bacteria to safely colonize the surface of medical implants, where it produced enzymes that dissolve superbug biofilms.

Staphylococcus aureus (or S. aureus) is a dangerous bacteria that’s increasingly picked up by patients in hospitals. It’s a hardy little bug that’s becoming resistant to almost all antibiotics, making it tricky to treat – especially when it shields itself behind protective biofilms. Medical implants like catheters, pacemakers and prosthetic joints are particularly susceptible to biofilm formation.

To bust down these defenses, researchers at the Centre for Genomic Regulation (CRG) in Spain developed a new potential treatment they call “living medicine.” The world of microbes is a brutal one, with bacteria battling each other for territory and resources, often by producing and releasing antimicrobial enzymes. So the team set out to use this to their advantage.

The starting point was a bacteria species called Mycoplasma pneumoniae, which was modified so that it wouldn’t cause illness in humans. Then it was engineered so that it could efficiently produce two enzymes that dissolve biofilms and the cell walls of bacteria within.

The team tested the technique by introducing colonies of M. pneumoniae to catheters infected with S. aureus biofilms. This was done in three different ways – in cell culture, in living mice, and by removing the catheter from mice, adding the treatment and then returning it to the body. In all three cases, infections were successfully treated, with the tests in living mice treating 82 percent of infections.

The researchers say there are a few specific benefits to using M. pneumoniae to break down biofilms. The species lacks cell walls, making them more efficient at releasing molecules and evading the host’s immune system. They also have a low risk of mutation and cannot transfer their modified genes to nearby microbes.

This means that the treatment should be safe for use in humans, which the team is beginning to prepare for.

“Our technology, based on synthetic biology and live biotherapeutics, has been designed to meet all safety and efficacy standards for application in the lung, with respiratory diseases being one of the first targets,” says María Lluch, co-corresponding author of the study. “Our next challenge is to address high-scale production and manufacturing, and we expect to start clinical trials in 2023.”

The research was published in the journal Molecular Systems Biology.

Source: Centre for Genomic Regulation