Advancing CRISPR antimicrobials to combat the bacterial pathogen Klebsiella pneumoniae
Therapeutics
- Chase Beisel, Helmholtz Centre for Infection Research, Germany (Coordinator)
- Udi Qimron, Tel-Aviv University, Israel (Partner)
- David Bikard, Institut Pasteur, France (Partner)
- Sylvain Brisse, Institut Pasteur, France (Partner)
- Strowig Till, Helmholtz Centre for Infection Research, Germany (Partner)
Multidrug-resistant bacterial infections are increasingly common, and the trickling pipeline of new antibiotics can do little to stem the tide. Instead, entirely new types of antibiotics are needed. One promising avenue involves CRISPR. CRISPR is best known for genome editing and a means to reverse genetic diseases. However, this same tool also be used to eliminate multidrug resistant pathogens while sparing commensal bacteria inhabiting our bodies. Early work highlighted the promise of these CRISPR antimicrobials, yet it remains a fledgling technology that requires further development before being ready for the clinic. Through funding from JPIAMR, we are developing CRISPR antimicrobials against Klebsiella pneumoniae, a major cause of multidrug resistant infections worldwide. These pathogens often spread in hospitals and can be resistant to virtually every antibiotic at our disposal. Our goals are to deliver CRISPR to these bacteria using bacterial viruses called bacteriophages and ensure CRISPR can eliminate cells carrying antibiotic resistance. Toward this goal, we have assembled a team of experts in CRISPR biology and technologies, bacteriophage engineering, and Klebsiella. The team has been engineering bacteriophages as vehicles to deliver the CRISPR cargo to different Klebsiella strains found in hospitals. We have also been identifying the best CRISPR enzymes that eradicate cells with target sequences. Finally, we are working toward experiments in mice that will lay a path toward clinical trials. The resulting optimized CRISPR antimicrobials will represent a leap forward toward the commercial development of novel antimicrobials against Klebsiella, and they will allow us to develop similar CRISPR antimicrobials against other multi-drug resistant pathogens. Through these efforts, we aim to provide new weapons against bacterial infections and turn the tide of antibiotic resistance.
