Gene-editing tool CRISPR repurposed to develop better antibiotics

A University of Wisconsin-Madison researcher and his collaborators at the University of California, San Francisco have repurposed the gene-editing tool CRISPR to study which genes are targeted by particular antibiotics, providing clues on how to improve existing antibiotics or develop new ones.

Resistance to current antibiotics by disease-causing pathogens is a growing problem, one estimated to endanger millions of lives and cost over $2 billion each year in the U.S.

"What we need to do is to figure out new weaknesses in these bacteria," says Jason Peters, a UW-Madison professor of pharmaceutical sciences, who developed the new system. The technique, known as Mobile-CRISPRi, allows scientists to screen for antibiotic function in a wide range of pathogenic bacteria.

Using a form of bacterial sex, the researchers transferred Mobile-CRISPRi from common laboratory strains into diverse bacteria, even including a little-studied microbe making its home on cheese rinds. This ease of transfer makes the technique a boon for scientists studying any number of bacteria that cause disease or promote health.

Peters worked with Carol Gross, Oren Rosenberg and other colleagues at UCSF and other institutions to design and test Mobile-CRISPRi. The system reduces the production of protein from targeted genes, allowing researchers to identify how antibiotics inhibit the growth of pathogens. That knowledge can help direct research to overcome resistance to existing drugs.