CRISPR Interference Tool Probes Antibiotic Resistance Genes
Investigators from the University of Wisconsin-Madison and the University of California have developed a new CRISPR tool to study which genes are targeted by particular antibiotics. Mobile-CRISPRi provides clues on how to improve existing drug compounds or develop new ones. This tool may prove to be very helpful in the battle against antimicrobial resistance.
Lead study investigator Jason Peters, from UW-Madison is the developer of this tool. He and his collaborators were working with CRISPRi, which just sits on DNA, making it impossible for other proteins to gain access to and turn on a particular gene. The result is a lower expression of the gene and a reduced amount of the protein it codes for.
“What that means is that you can now do studies on how antibiotics work directly in these pathogens. That could give us a better clue about how these drugs work in the different organisms and potentially what we can do to make them better” says Peters.
His research team made CRISPRi mobile by developing methods to transfer the system from common lab models to disease-causing species. Peters’ team turned to one of the natural ways in which bacteria link up and exchange DNA, called ‘conjugation’. “You basically mix the bacteria and it happens,” Peters commented. “It doesn’t get much easier than that.”
This transfer is so efficient that it makes the technique a benefit for scientists studying any number of bacteria that cause disease or promote health. Also, the system lessens the targeted genes’ protein production, which allows researchers to identify the way antibiotics restrain the growth of pathogens. Research to overcome resistance to existing drugs can be supported by this knowledge.
With this study, researchers showed that decreasing the amount of protein targeted by an antibiotic makes bacteria more sensitive to lower levels of the drug. This proves there is an association between gene and drug. Knowing this, scientists can screen thousands of genes at a time as potential antibiotic targets, which helps them learn how antibiotics work and can be improved.