Pandemic spread of blaKPC-2 among Klebsiella pneumoniae ST11 in China is associated with horizontal transfer mediated by IncFII-like plasmids

Abstract Objectives This study aimed to investigate the spread of the bla KPC-2 gene among Klebsiella pneumoniae and to illustrate the mechanism of dissemination of KPC-producing K. pneumoniae (KPC- Kp ) ST11 in China. Methods A total of 354 K. pneumoniae isolates were collected from four hospitals in China and were characterized by Multilocus sequence typing (MLST). Mobile genetic elements (MGEs) and pulsed-field gel electrophoresis (PFGE) analysis were used to identify the subtypes of K. pneumoniae ST11. PCR-based amplification and sequencing were performed to analyze Tn 1721 transposons and IncFII-like plasmids. Electroporation experiments and whole-genome sequencing (WGS) analysis were used to reveal the genetic environment of the bla KPC-2 gene. Results As the primary type(87.1%) of KPC- Kp, K. pneumoniae ST11 was not predominant in nonKPC- Kp (3.1%). ST11 KPC- Kp was clonally heterogeneous and could be further classified into eleven MGE types and fourteen PFGE subtypes. Five Tn 1721 - bla KPC-2 variants were identified on IncFII-like plasmids. The detection rate of IncFII-like plasmids was much higher in ST11 KPC- Kp (100%) compared with non-ST11 KPC- Kp (16.0%) and the nonKPC- Kp group (7.5%). Moreover, the IncFII plasmid (with II a replicon) was primarily detected on the MGE-F type (61.7%). The IncFII k plasmid (with II k replicon) was clustered into two subtypes: MGE-A (28.3%) and -F (41.5%). The detection of the IncFII and IncFII k plasmids on MGE-A was 57.1% (20/35) and 42.9% (15/35), respectively. Conclusions We revealed a close correlation between ST11 KPC- Kp and IncFII-like plasmids. Horizontal transfer mediated by IncFII-like plasmids plays an important role in the pandemic expansion of bla KPC-2 among K. pneumoniae ST11 in China.