Gene-editing method to kill antibiotic-resistant bugs

US engineers have developed a new gene-editing system that can selectively kill bacteria carrying harmful genes that confer antibiotic resistance or cause disease.

"We have been interested in finding new ways to combat antibiotic resistance and this method offers new strategies to achieve that," said Timothy Lu, an associate professor of biological engineering, electrical engineering and computer science at the Massachusetts Institute of Technology (MIT).

In the new study, researchers targeted specific genes that allow bacteria to survive antibiotic treatment.

The CRISPR genome-editing system presented the perfect strategy to go after those genes.

CRISPR, originally discovered by biologists studying the bacterial immune system, involves a set of proteins that bacteria use to defend themselves against bacteriophages (viruses that infect bacteria).

One of these proteins, a DNA-cutting enzyme called Cas9, binds to short RNA guide strands telling Cas9 where to make its cuts.

Lu and colleagues decided to turn bacteria's own weapons against them.

They designed their RNA guide strands to target genes for antibiotic resistance, including the enzyme NDM-1, which allows bacteria to resist a broad range of beta-lactam antibiotics.

When the researchers turned the CRISPR system against NDM-1, they were able to specifically kill more than 99 percent of NDM-1-carrying bacteria, while antibiotics to which the bacteria were resistant did not induce any significant killing.

In addition, the researchers showed that the CRISPR system could be used to selectively remove specific bacteria from diverse bacterial communities based on their genetic signatures, thus opening up the potential for "microbiome editing" beyond antimicrobial applications.

"The technology could be adapted to deliver the CRISPR components to treat infections or remove other unwanted bacteria in human patients," Lu noted.

The findings appeared in the journal Nature Biotechnology.