The type I-E CRISPR-Cas system influences the acquisition of bla(KPC)-IncF plasmid in Klebsiella pneumonia

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) have disseminated worldwide and emerged as major threats to public health. Of epidemiological significance, the international pandemic of KPC-KP is primarily associated with CG258 isolates and bla(KPC)-IncF plasmids. CRISPR-Cas system is an adaptive immune system that can hinder gene expansion driven by horizontal gene transfer. Because of bla(KPC)-IncF plasmids are favored by CG258 K. pneumoniae, it was of interest to examine the co-distribution of CRISPR and bla(KPC)-IncF plasmids in such isolates. We collected 459 clinical K. pneumoniae isolates in China and collected 203 global whole-genome sequences in GenBank to determine the prevalence of CRISPR-Cas systems. We observed that CRISPR-Cas system was significantly scarce in the CG258 lineage and bla(KPC)-positive isolates. Furthermore, the results of conjugation and plasmid stability assay fully demonstrated the CRIPSR-Cas system in K. pneumoniae could effectively hindered bla(KPC)-IncF plasmids invasion and existence. Notably, most bla(KPC)-IncF plasmids were also proved to be good targets of CRISPR owing to carry matched and functional protospacers and PAMs. Overall, our work suggests that type I-E CRISPR-Cas systems could impact the spread of bla(KPC) in K. pneumoniae populations, and the scarcity of CRISPR-Cas system was one of potential factors leading to the propagation of bla(KPC)-IncF plasmids in CG258 K. pneumoniae.