Multiple benefits of plasmid-mediated quinolone resistance determinants in klebsiella pneumoniae ST11 high-risk clone and recently emerging ST307 clone

Judit Domokos, Ivelina Damjanova, Katalin Kristof, Balazs Ligeti, B. Kocsis, D. Szabó

Research output: Contribution to journalArticle

Abstract

International high-risk clones of Klebsiella pneumoniae are among the most common nosocomial pathogens. Increased diversity of plasmid-encoded antimicrobial resistance genes facilitates spread of these clones causing significant therapeutic difficulties. The purpose of our study was to investigate fluoroquinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing strains, including four K. pneumoniae and a single K. oxytoca, isolated from blood cultures in Hungary. Whole-genome sequencing and molecular typing including multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed in selected strains. Gene expression of plasmid-mediated quinolone resistance determinants (PMQR) was investigated by quantitative-PCR. MLST revealed that three K. pneumoniae strains belonged to ST11 and one to ST307 whereas K. oxytoca belonged to ST52. The isolates harbored different β-lactamase genes, however, all K. pneumoniae uniformly carried bla CTX-M-15 . The K. pneumoniae isolates exhibited resistance to fluoroquinolones and carried various PMQR genes namely, two ST11 strains harbored qnrB4, the ST307 strain harbored qnrB1 and all K. pneumoniae harbored oqxAB efflux pump. Levofloxacin and moxifloxacin MIC values of K. pneumoniae ST11 and ST307 clones correlated with qnr and oqxAB expression levels. The qnrA1 carrying K. oxytoca ST52 exhibited reduced susceptibility to fluoroquinolones. The maintained expression of qnr genes in parallel with chromosomal mutations indicate an additional protective role of Qnr proteins that can support dissemination of high-risk clones. During development of high-level fluoroquinolone resistance, high-risk clones retain fitness thus, enabling them for dissemination in hospital environment. Based on our knowledge this is the first report of ST307 clone in Hungary, that is emerging as a potential high-risk clone worldwide. High-level fluoroquinolone resistance in parallel with upregulated PMQR gene expression are linked to high-risk K. pneumoniae clones.

Original languageEnglish
Article number00157
JournalFrontiers in Microbiology
Volume10
Issue numberFEB
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Quinolones
Klebsiella pneumoniae
Plasmids
Clone Cells
Fluoroquinolones
Multilocus Sequence Typing
Hungary
Gene Expression
Genes
Molecular Typing
Levofloxacin
Pulsed Field Gel Electrophoresis
beta-Lactamases
Genome
Polymerase Chain Reaction
Mutation

Keywords

  • Gene expression
  • International clones
  • Multi-drug resistance
  • Plasmid-mediated quinolone resistance
  • Whole genome sequence analysis

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Multiple benefits of plasmid-mediated quinolone resistance determinants in klebsiella pneumoniae ST11 high-risk clone and recently emerging ST307 clone. / Domokos, Judit; Damjanova, Ivelina; Kristof, Katalin; Ligeti, Balazs; Kocsis, B.; Szabó, D.

In: Frontiers in Microbiology, Vol. 10, No. FEB, 00157, 01.01.2019.

Research output: Contribution to journalArticle

@article{4be432ab1f02409e83a9861bb454a79e,
title = "Multiple benefits of plasmid-mediated quinolone resistance determinants in klebsiella pneumoniae ST11 high-risk clone and recently emerging ST307 clone",
abstract = "International high-risk clones of Klebsiella pneumoniae are among the most common nosocomial pathogens. Increased diversity of plasmid-encoded antimicrobial resistance genes facilitates spread of these clones causing significant therapeutic difficulties. The purpose of our study was to investigate fluoroquinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing strains, including four K. pneumoniae and a single K. oxytoca, isolated from blood cultures in Hungary. Whole-genome sequencing and molecular typing including multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed in selected strains. Gene expression of plasmid-mediated quinolone resistance determinants (PMQR) was investigated by quantitative-PCR. MLST revealed that three K. pneumoniae strains belonged to ST11 and one to ST307 whereas K. oxytoca belonged to ST52. The isolates harbored different β-lactamase genes, however, all K. pneumoniae uniformly carried bla CTX-M-15 . The K. pneumoniae isolates exhibited resistance to fluoroquinolones and carried various PMQR genes namely, two ST11 strains harbored qnrB4, the ST307 strain harbored qnrB1 and all K. pneumoniae harbored oqxAB efflux pump. Levofloxacin and moxifloxacin MIC values of K. pneumoniae ST11 and ST307 clones correlated with qnr and oqxAB expression levels. The qnrA1 carrying K. oxytoca ST52 exhibited reduced susceptibility to fluoroquinolones. The maintained expression of qnr genes in parallel with chromosomal mutations indicate an additional protective role of Qnr proteins that can support dissemination of high-risk clones. During development of high-level fluoroquinolone resistance, high-risk clones retain fitness thus, enabling them for dissemination in hospital environment. Based on our knowledge this is the first report of ST307 clone in Hungary, that is emerging as a potential high-risk clone worldwide. High-level fluoroquinolone resistance in parallel with upregulated PMQR gene expression are linked to high-risk K. pneumoniae clones.",
keywords = "Gene expression, International clones, Multi-drug resistance, Plasmid-mediated quinolone resistance, Whole genome sequence analysis",
author = "Judit Domokos and Ivelina Damjanova and Katalin Kristof and Balazs Ligeti and B. Kocsis and D. Szab{\'o}",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fmicb.2019.00157",
language = "English",
volume = "10",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media S. A.",
number = "FEB",

}

TY - JOUR

T1 - Multiple benefits of plasmid-mediated quinolone resistance determinants in klebsiella pneumoniae ST11 high-risk clone and recently emerging ST307 clone

AU - Domokos, Judit

AU - Damjanova, Ivelina

AU - Kristof, Katalin

AU - Ligeti, Balazs

AU - Kocsis, B.

AU - Szabó, D.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - International high-risk clones of Klebsiella pneumoniae are among the most common nosocomial pathogens. Increased diversity of plasmid-encoded antimicrobial resistance genes facilitates spread of these clones causing significant therapeutic difficulties. The purpose of our study was to investigate fluoroquinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing strains, including four K. pneumoniae and a single K. oxytoca, isolated from blood cultures in Hungary. Whole-genome sequencing and molecular typing including multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed in selected strains. Gene expression of plasmid-mediated quinolone resistance determinants (PMQR) was investigated by quantitative-PCR. MLST revealed that three K. pneumoniae strains belonged to ST11 and one to ST307 whereas K. oxytoca belonged to ST52. The isolates harbored different β-lactamase genes, however, all K. pneumoniae uniformly carried bla CTX-M-15 . The K. pneumoniae isolates exhibited resistance to fluoroquinolones and carried various PMQR genes namely, two ST11 strains harbored qnrB4, the ST307 strain harbored qnrB1 and all K. pneumoniae harbored oqxAB efflux pump. Levofloxacin and moxifloxacin MIC values of K. pneumoniae ST11 and ST307 clones correlated with qnr and oqxAB expression levels. The qnrA1 carrying K. oxytoca ST52 exhibited reduced susceptibility to fluoroquinolones. The maintained expression of qnr genes in parallel with chromosomal mutations indicate an additional protective role of Qnr proteins that can support dissemination of high-risk clones. During development of high-level fluoroquinolone resistance, high-risk clones retain fitness thus, enabling them for dissemination in hospital environment. Based on our knowledge this is the first report of ST307 clone in Hungary, that is emerging as a potential high-risk clone worldwide. High-level fluoroquinolone resistance in parallel with upregulated PMQR gene expression are linked to high-risk K. pneumoniae clones.

AB - International high-risk clones of Klebsiella pneumoniae are among the most common nosocomial pathogens. Increased diversity of plasmid-encoded antimicrobial resistance genes facilitates spread of these clones causing significant therapeutic difficulties. The purpose of our study was to investigate fluoroquinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing strains, including four K. pneumoniae and a single K. oxytoca, isolated from blood cultures in Hungary. Whole-genome sequencing and molecular typing including multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed in selected strains. Gene expression of plasmid-mediated quinolone resistance determinants (PMQR) was investigated by quantitative-PCR. MLST revealed that three K. pneumoniae strains belonged to ST11 and one to ST307 whereas K. oxytoca belonged to ST52. The isolates harbored different β-lactamase genes, however, all K. pneumoniae uniformly carried bla CTX-M-15 . The K. pneumoniae isolates exhibited resistance to fluoroquinolones and carried various PMQR genes namely, two ST11 strains harbored qnrB4, the ST307 strain harbored qnrB1 and all K. pneumoniae harbored oqxAB efflux pump. Levofloxacin and moxifloxacin MIC values of K. pneumoniae ST11 and ST307 clones correlated with qnr and oqxAB expression levels. The qnrA1 carrying K. oxytoca ST52 exhibited reduced susceptibility to fluoroquinolones. The maintained expression of qnr genes in parallel with chromosomal mutations indicate an additional protective role of Qnr proteins that can support dissemination of high-risk clones. During development of high-level fluoroquinolone resistance, high-risk clones retain fitness thus, enabling them for dissemination in hospital environment. Based on our knowledge this is the first report of ST307 clone in Hungary, that is emerging as a potential high-risk clone worldwide. High-level fluoroquinolone resistance in parallel with upregulated PMQR gene expression are linked to high-risk K. pneumoniae clones.

KW - Gene expression

KW - International clones

KW - Multi-drug resistance

KW - Plasmid-mediated quinolone resistance

KW - Whole genome sequence analysis

UR - http://www.scopus.com/inward/record.url?scp=85065890822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065890822&partnerID=8YFLogxK

U2 - 10.3389/fmicb.2019.00157

DO - 10.3389/fmicb.2019.00157

M3 - Article

VL - 10

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

IS - FEB

M1 - 00157

ER -