Dr. Beisel and Colleagues Develop Potential Prototype for a New Class of Antibiotics

Dr. Chase Beisel and fellow researchers have developed what might be the prototype for a new class of antibiotics. According to Dr. Beisel, senior author of a paper describing the work, “Conventional antibiotic treatments kill both ‘good’ and ‘bad’ bacteria, leading to unintended consequences, such as opportunistic infections.” “What we’ve shown in this new work is that it is possible to selectively remove specific strains of bacteria without affecting populations of good bacteria.”

The new approach works by taking advantage of a part of the immune system present in many bacteria called the CRISPR-Cas system. CRISPR-Cas protects bacteria from invaders such as viruses by creating small strands of RNA called CRISPR RNA that match DNA sequences specific to a given invader. When those CRISPR RNAs find a match, they engage Cas proteins that cut the DNA.

“This sets the stage for next-generation antibiotics using programmable CRISPR-Cas systems,” says CRISPR pioneer, Dr. Rodolphe Barrangou, a co-author of the manuscript. While working at the cheese and yogurt manufacturer, Danisco, Dr. Barrangou and his colleagues combined their lab results with knowledge from three other independent research groups to publish a seminal paper in 2007, showing that a bacterium could be engineered to either resist or succumb to attack from phages by altering its CRISPR-Cas system.

Dr. Beisel and fellow researchers have demonstrated that designing CRISPR RNAs to target DNA sequences in the bacteria themselves causes bacterial suicide, as a bacterium’s CRISPR-Cas system attacks its own DNA. “In lab testing, we found that this approach removes the targeted bacteria,” Beisel says. “We’re excited by the ease in specifically targeting different bacteria and the potency of elimination.”

The researchers tested the approach in controlled cultures with different combinations of bacteria present, and were able to eliminate only the targeted strain. “For example, we were able to eliminate Salmonella in a culture without affecting good bacteria normally found in the digestive tract,” Beisel says. The researchers were also able to demonstrate the precision of the technique by eliminating one strain of a species, but not another strain of the same species which shares 99 percent of the same DNA.

Another benefit of the approach, Beisel says, is that “by targeting specific DNA strands through the CRISPR-Cas system, we’re able to bypass antibiotic resistance.” The technique offers a potential approach to treat infections caused by multi-drug resistant “super bugs” such as MRSA. The researchers are currently working to develop effective methods for delivering the CRISPR RNAs in clinical settings.

The work has spawned a company, Locus Biosciences. Drs. Barrangou and Beisel are two of its co-founders and serve as members of the Scientific Advisory Board.

Dr. Beisel is an assistant professor of chemical and biomolecular engineering. Dr. Barrangou is an associate professor of food, bioprocessing and nutrition sciences. Lead author of the paper, “Programmable Removal of Bacterial Strains by Use of Genome-Targeting CRISPR-Cas Systems” is Ahmed Abdelshafy Gooma, a CBE Ph.D. graduate. Co-authors include Heidi Klumpe, a former CBE undergraduate, Michelle Luo, a CBE Ph.D. student, and Kurt Selle, a FBNS Ph.D. student. The work was reported in Nature, the New York Times, ScienceNews, and Faculty of 1000.