Characterization of a blaNDM-1-Bearing IncHI5-Like Plasmid From Klebsiella pneumoniae of Infant Origin

Abstract

The spread of plasmid-mediated carbapenem-resistant clinical isolates is a serious threat to global health. In this study, an emerging NDM-encoding IncHI5-like plasmid from <i>Klebsiella pneumoniae</i> of infant patient origin was characterized, and the plasmid was compared to the available IncHI5-like plasmids to better understand the genetic composition and evolution of this emerging plasmid. Clinical isolate C39 was identified as <i>K. pneumoniae</i> and belonged to the ST37 and KL15 serotype. Whole genome sequencing (WGS) and analysis revealed that it harbored two plasmids, one of which was a large IncHI5-like plasmid pC39-334kb encoding a wide variety of antimicrobial resistance genes clustered in a single multidrug resistance (MDR) region. The <i>bla</i>_NDM-1 gene was located on a ΔIS<i>Aba125</i>-<i>bla</i>_NDM-1-<i>ble</i>_MBL-<i>trpF</i>-<i>dsbC</i> structure. Comparative genomic analysis showed that it shared a similar backbone with four IncHI5-like plasmids and the IncHI5 plasmid pNDM-1-EC12, and these six plasmids differed from typical IncHI5 plasmids. The replication genes of IncHI5-like plasmids shared 97.06% (<i>repHI5B</i>) and 97.99% (<i>repFIB-like</i>) nucleotide identity with those of IncHI5 plasmids. Given that pNDM-1-EC12 and all IncHI5-like plasmids are closely related genetically, the occurrence of IncHI5-like plasmid is likely associated with the mutation of the replication genes of pNDM-1-EC12-like IncHI5 plasmids. All available IncHI5-like plasmids harbored 262 core genes encoding replication and maintenance functions and carried distinct MDR regions. Furthermore, 80% of them (4/5) were found in <i>K. pneumoniae</i> from Chinese nosocomial settings. To conclude, this study expands our knowledge of the evolution history of IncHI5-like plasmids, and more attention should be paid to track the evolution pathway of them among clinical, animal, and environmental settings.