Wednesday, 6 February 2019

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.

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.

The researchers showed that if they decreased the amount of protein targeted by an antibiotic, bacteria became much more sensitive to lower levels of the drug -- evidence of an association between gene and drug. Thousands of genes at a time can be screened as potential antibiotic targets this way, helping scientists learn how antibiotics work and how to improve them.

To make CRISPRi mobile, the researchers developed methods to transfer the system from common lab models like E. coli to disease-causing species, which are often harder to study. Peters' team turned to one of the natural ways bacteria link up and exchange DNA, a kind of bacterial sex called conjugation.


Jason M. Peters, Byoung-Mo Koo, Ramiro Patino, Gary E. Heussler, Cameron C. Hearne, Jiuxin Qu, Yuki F. Inclan, John S. Hawkins, Candy H. S. Lu, Melanie R. Silvis, M. Michael Harden, Hendrik Osadnik, Joseph E. Peters, Joanne N. Engel, Rachel J. Dutton, Alan D. Grossman, Carol A. Gross, Oren S. Rosenberg. Enabling genetic analysis of diverse bacteria with Mobile-CRISPRi. Nature Microbiology, 2019; DOI: 10.1038/s41564-018-0327-z

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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