Antibiotics are typically life-saving heroes, but they can sometimes backfire—especially when dealing with the notorious Shiga toxin-producing E. coli. When these bacteria die, they unleash a torrent of lethal toxins. Enter a groundbreaking new approach that flips this dangerous script.

A team of innovators, led by Harris Wang at Columbia University, has developed a cutting-edge gene-editing technique called Bacterial CRISPR–Transposase Reduction of Virulence In Situ, or BACTRINS. Instead of wiping out these harmful bacteria, BACTRINS cleverly reprograms them to cease toxin production and even generate beneficial molecules.

Here’s how it works: This ingenious system employs a combination of CRISPR-Cas technology and transposases, targeting the genes responsible for the Shiga toxin—namely stx1 and stx2. Using specific guide RNAs, the CRISPR-Cas complex zeroes in on mutation-resistant regions of these genes. A transposase then introduces new DNA that disrupts the harmful gene, all while sparing the bacterial genome from damage.

Wang proudly states, "We’re essentially converting a pathogenic strain into a nonpathogenic one.” This innovative approach means no toxins leak into the gut, and importantly, it bypasses the DNA repair mechanisms that often lead to treatment resistance.

To amplify this method's effectiveness, the researchers ingeniously engineered the inserted DNA to produce nanobodies—tiny proteins that combat E. coli by binding to a surface protein called Tir. Without a functional Tir, these bacteria struggle to invade and infect the gut.

BACTRINS works by first introducing the system into benign bacteria. Once the engineered bacteria are consumed, they serve as a delivery system, sharing the genetic modifications with harmful strains through a natural process called bacterial conjugation.

In tantalizing trials with mice infected by the deadly E. coli strain, untreated subjects faced grim fates, while those treated with BACTRINS saw toxin levels plummet by two-thirds, significantly improving survival rates. Although some treated mice still succumbed, Wang notes that the bacterial strain used is more lethal to mice than humans, suggesting promising implications for human health.

Bacterial pathogenesis expert Byeonghwa Jeon from the University of Minnesota applauds the study’s potential but stresses that further research is essential before BACTRINS can make it to the clinic.

Wang envisions that this innovative BACTRINS platform could be adapted for various bacteria across different body systems, or even for beneficial soil microbes. The team is excited to explore these avenues and aims to harness the system to enhance the positive effects of friendly bacteria. "This adds to our genetic toolkit and could be applicable in many different scenarios," Wang concludes.