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

Abstract

ObjectivesThe aim of this study was to investigate the spread of the blaKPC-2 gene among Klebsiella pneumoniae and to illustrate the mechanism of dissemination of K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) ST11 in China. MethodsA 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. Polymerase chain reaction (PCR)-based amplification and sequencing were performed to analyse Tn1721 transposons and IncFII-like plasmids. Electroporation experiments and whole-genome sequencing (WGS) were used to reveal the genetic environment of the blaKPC-2 gene. ResultsAs the primary type (87.1%) of KPC-Kp, K. pneumoniae ST11 was not predominant in non-KPC-Kp (3.1%). ST11 KPC-Kp was clonally heterogeneous and could be further classified into 11 MGE types and 14 PFGE subtypes. Five Tn1721-blaKPC-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 non-KPC-Kp group (7.5%). Moreover, the IncFII plasmid (with IIa replicon) was primarily detected on the MGE-F type (61.7%). The IncFIIk plasmid (with IIk replicon) was clustered into two subtypes: MGE-A (28.3%) and -F (41.5%). The detection of the IncFII and IncFIIk plasmids on MGE-A was 57.1% (20/35) and 42.9% (15/35), respectively. ConclusionsA close correlation was shown between ST11 KPC-Kp and IncFII-like plasmids. Horizontal transfer mediated by IncFII-like plasmids plays an important role in the pandemic expansion of blaKPC-2 among K. pneumoniae ST11 in China.