Project: Advancing CRISPR antimicrobials to combat the bacterial pathogen Klebsiella pneumoniae

Acronym CRISPRattacK (Reference Number: JPIAMR_2018_P002)
Duration 01/01/2019 - 31/12/2020
Project Topic The increasing incidence of multidrug-resistant bacterial infections and the trickling pipeline of novel antibiotic classes demand a new generation of antimicrobials. One promising avenue has been the development of antimicrobials based on CRISPR-Cas immune systems. These systems can be programmed to specifically and efficiently eliminate cells harbouring multi-drug resistance genes without impinging on resident microbiota. However, CRISPR antimicrobials remain to be advanced from a few proof-of-principle demonstrations to established therapeutics that can effectively combat the most pressing pathogens. Here, we propose to advance this antimicrobial platform to selectively kill Klebsiella pneumoniae, a major cause of multi-drug resistant, nosocomial infections worldwide. We have devised a series of experimental approaches that will identify the most active CRISPR nucleases and DNA target sites for programmed killing, engineer bacteriophage delivery vehicles that can efficiently deliver CRISPR to a large fraction of clinical isolates, and evaluate the efficacy of the most promising therapeutic candidates in mouse infection models. Once demonstrated, the resulting optimised CRISPR antimicrobials will represent a large leap forward for the development of novel antimicrobials against Klebsiella, and they will provide a framework to develop similar antimicrobials against other high-priority pathogens associated with multidrug resistance.
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Network JPI AMR
Call 6th Joint Call of JPIAMR

Project partner

Number Name Role Country
1 Helmholtz Institute for RNA-based Infection Research Coordinator Germany
1 Tel Aviv University Partner Israel
2 Pasteur Institute Partner France
3 Pasteur Institute Partner France
4 Helmholtz Center for Infection Research Partner Germany