Expansion of KPC-producing Klebsiella pneumoniae with various mgrB mutations giving rise to colistin resistance: the role of ISL3 on plasmids

•mgrB was disrupted at identical nucleotide positions in different lineages, showing that ISL3 recombines at specific sites.•Frequent insertion of ISL3 in mgrB and other inner membrane proteins suggest that these are hotspots for ISL3 integration.•The ISL3-carrying pKpQIL-like plasmid is omnipresent...

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Bibliographic Details
Published in:International journal of antimicrobial agents 2018-02, Vol.51 (2), p.260-265
Main Authors: Giordano, Cesira, Barnini, Simona, Tsioutis, Constantinos, Chlebowicz, Monika A., Scoulica, Effie V., Gikas, Achilleas, Rossen, John W., Friedrich, Alexander W., Bathoorn, Erik
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
beta-Lactamases - genetics
Colistin
Colistin - pharmacology
DNA Transposable Elements - genetics
Drug Resistance, Bacterial - genetics
Genome, Bacterial - genetics
Greece
Humans
ISL3
Italy
Klebsiella pneumoniae
Klebsiella pneumoniae - drug effects
Klebsiella pneumoniae - genetics
Klebsiella pneumoniae - isolation & purification
KPC
Membrane Proteins - genetics
mgrB
Molecular epidemiology
Plasmids - genetics
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Summary:•mgrB was disrupted at identical nucleotide positions in different lineages, showing that ISL3 recombines at specific sites.•Frequent insertion of ISL3 in mgrB and other inner membrane proteins suggest that these are hotspots for ISL3 integration.•The ISL3-carrying pKpQIL-like plasmid is omnipresent in KPC-producing Klebsiella pneumoniae (KPC-KP).•Both horizontal transmission by plasmids and vertical clonal expansion of colistin resistance was observed.•Both represent important epidemiological explanations for emergence of colistin resistance in KPC-KP in Southern Europe. mcr-1 has been reported as the first plasmid-encoded gene conferring colistin resistance. In KPC-producing Klebsiella pneumoniae (KPC-KP), however, colistin resistance is rapidly emerging through other mechanisms. Resistance is frequently due to disruption of the mgrB gene by insertion sequences, e.g. ISL3. The aim of this study was to investigate the expansion of mgrB-mutated KPC-KP isolates. In addition, the localisation and targets of ISL3 sequences within the core and accessory genome of common KPC-KP lineages were identified. A total of 29 clinical K. pneumoniae isolates collected from Italian patients were randomly selected. Whole genome sequences were analysed for resistance genes, plasmids and insertion sequences. In addition, 27 colistin-resistant KPC-KP isolates from a previous study from Crete (Greece) were assessed. Clonal expansion of KPC-KP isolates with various mutations in mgrB among all lineages was observed. In two Italian MLST ST512 isolates and eight Greek ST258 isolates, an identical copy of ISL3 was inserted in mgrB nucleotide position 133. ISL3, a transposable restriction–modification system of 8154 nucleotides, was located on pKpQIL-like plasmids and may transpose into the chromosome. In four isolates, chromosomal integration of ISL3 in diverse inner membrane proteins other than mgrB was identified. Colistin resistance is most often explained by clonal expansion of isolates with mutated mgrB. pKpQIL-like plasmids, which are omnipresent in KPC-KP, carry insertion sequences such as ISL3 that have mgrB as a target hotspot for transposition. Transposition of insertion sequences from plasmids and subsequent clonal expansion may contribute to the emerging colistin resistance in KPC-KP.
ISSN:0924-8579
1872-7913
DOI:10.1016/j.ijantimicag.2017.10.011