Exploiting a conjugative endogenous CRISPR-Cas3 system to tackle multidrug-resistant Klebsiella pneumoniae.

ABSTRACT:

Background

Mobile plasmids play a key role in spurring the global dissemination of multidrug-resistant (MDR) K. pneumoniae, while plasmid curing has been recognized as a promising strategy to combat antimicrobial resistance. Here we exploited a K. pneumoniae native CRISPR system to cure the high-risk IncFII plasmids.

Methods

We examined matched protospacers in 725 completely sequenced IncFII plasmids from K. pneumoniae genomes. Then, we re-engineered a native CRISPR-Cas3 system and deliver the CRISPR-Cas3 system via conjugation. Plasmid killing efficiency and G. mellonella infection model were applied to evaluate the CRISPR-Cas3 immunity in vitro and in vivo.

Findings

Genomic analysis revealed that most IncFII plasmids could be targeted by the native CRISPR-Cas3 syste

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC9879765 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature