AUTHOR=Domokos Judit , Damjanova Ivelina , Kristof Katalin , Ligeti Balazs , Kocsis Bela , Szabo Dora 

TITLE=Multiple Benefits of Plasmid-Mediated Quinolone Resistance Determinants in Klebsiella pneumoniae ST11 High-Risk Clone and Recently Emerging ST307 Clone

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00157

DOI=10.3389/fmicb.2019.00157

ISSN=1664-302X

ABSTRACT=<p>International high-risk clones of <italic>Klebsiella pneumoniae</italic> 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 <italic>K. pneumoniae</italic> and a single <italic>K. oxytoca</italic>, 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 <italic>K. pneumoniae</italic> strains belonged to ST11 and one to ST307 whereas <italic>K</italic>. <italic>oxytoca</italic> belonged to ST52. The isolates harbored different β-lactamase genes, however, all <italic>K. pneumoniae</italic> uniformly carried <italic>bla</italic><sub>CTX-M-15</sub>. The <italic>K. pneumoniae</italic> isolates exhibited resistance to fluoroquinolones and carried various PMQR genes namely, two ST11 strains harbored <italic>qnrB4</italic>, the ST307 strain harbored <italic>qnrB1</italic> and all <italic>K. pneumoniae</italic> harbored <italic>oqxAB</italic> efflux pump. Levofloxacin and moxifloxacin MIC values of <italic>K. pneumoniae</italic> ST11 and ST307 clones correlated with <italic>qnr</italic> and <italic>oqxAB</italic> expression levels. The <italic>qnrA1</italic> carrying <italic>K. oxytoca</italic> ST52 exhibited reduced susceptibility to fluoroquinolones. The maintained expression of <italic>qnr</italic> 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 <italic>K. pneumoniae</italic> clones.</p>