Abstract
Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.
Highlights
The evolution and spread of antibiotic-resistant pathogens has emerged as one of the most important public health problems worldwide over the last decades
9/42 OXA-48, 3/34 KPC-2- and 1/5 NDM-1-producing isolates were assigned to ST147 [19]
Comparative analysis revealed a rearrangement of a composite transposon flanked by two inverted copies of IS26 and containing catB3-like, aac(6’)Ib-cr and blaOXA-1 genes. This 3826 bp region was inserted in the same position in the two IncR plasmids but in opposite orientation
Summary
The evolution and spread of antibiotic-resistant pathogens has emerged as one of the most important public health problems worldwide over the last decades (https://www.who.int/en/newsroom/fact-sheets/detail/antibiotic-resistance). Plasmids are often assemblies of different MGE modules and are the most efficient intra- and interspecies DNA transfer mechanism among prokaryotes [2]. This is well exemplified by the global spread of the KPC carbapenemase involving the incompatibility group FIIk (IncFIIk) plasmids in Klebsiella pneumoniae [3]. K. pneumoniae ST147 has been reported as an emerging high-risk clone associated with plasmid-encoded extended-spectrum β-lactamases (ESBLs) like blaCTX-M-15, or carbapenemases such as blaOXA-48 and blaNDM-1 [4,12,13,14,15,16,17]. We characterise the content and genetic structure of MGEs and the clonal relatedness of three OXA-181-producing K. pneumoniae ST147 clinical isolates recovered in Germany
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
