The type I-E CRISPR-Cas system influences the acquisition of <i>bla</i> _KPC -IncF plasmid in <i>Klebsiella pneumonia</i>

Abstract

<i>Klebsiella pneumoniae</i> carbapenemase (KPC)-producing <i>K. pneumoniae</i> (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 <i>bla</i>_KPC-IncF plasmids. CRISPR-Cas system is an adaptive immune system that can hinder gene expansion driven by horizontal gene transfer. Because of <i>bla</i>_KPC-IncF plasmids are favored by CG258 <i>K. pneumoniae,</i> it was of interest to examine the co-distribution of CRISPR and <i>bla</i>_KPC-IncF plasmids in such isolates. We collected 459 clinical <i>K. pneumoniae isolates</i> 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 <i>bla</i>_KPC-positive isolates. Furthermore, the results of conjugation and plasmid stability assay fully demonstrated the CRIPSR-Cas system in <i>K. pneumoniae</i> could effectively hindered <i>bla</i>_KPC-IncF plasmids invasion and existence. Notably, most <i>bla</i>_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 <i>bla</i>_KPC in <i>K. pneumoniae</i> populations, and the scarcity of CRISPR-Cas system was one of potential factors leading to the propagation of <i>bla</i>_KPC-IncF plasmids in CG258 <i>K. pneumoniae</i>.