High-efficiency delivery of CRISPR-Cas9 by engineered probiotics enables precise microbiome editing.

ABSTRACT: Antibiotic resistance threatens our ability to treat infectious diseases, spurring interest in alternative antimicrobial technologies. The use of bacterial conjugation to deliver CRISPR-cas systems programmed to precisely eliminate antibiotic-resistant bacteria represents a promising approach but requires high in situ DNA transfer rates. We have optimized the transfer efficiency of conjugative plasmid TP114 using accelerated laboratory evolution. We hence generated a potent conjugative delivery vehicle for CRISPR-cas9 that can eliminate > 99.9% of targeted antibiotic-resistant Escherichia coli in the mouse gut microbiota using a single dose. We then applied this system to a Citrobacter rodentium infection model, achieving full clearance within four consecutive days of treatment.

SUBMITTER: Neil K 

PROVIDER: S-EPMC8527022 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature