Factors influencing the expression of plasmid-mediated quinolone determinants (PMQRs)  Page description

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Details of project

 
Identifier
108481
Type K
Principal investigator Szabó, Dóra
Title in Hungarian A plazmid mediálta kinolon rezisztencia determinánsok kifejeződését befolyásoló tényezők vizsgálata
Title in English Factors influencing the expression of plasmid-mediated quinolone determinants (PMQRs)
Keywords in Hungarian kinolon, plazmid-mediálta rezisztencia, génexpresszió, kísérletes állatmodell
Keywords in English quinolone, plasmid.mediated resistance, gene expression, experimental animal model
Discipline
Microbiology: virology, bacteriology, parasitology, mycology (Council of Medical and Biological Sciences)100 %
Panel Immunity, Cancer and Microbiology
Department or equivalent Dept. of Medical Microbiology (Semmelweis University)
Participants Göcző, István
Ivády, Balázs
Kocsis, Béla
Kristóf, Katalin
Szmolka, Annamária
Starting date 2013-09-01
Closing date 2018-08-31
Funding (in million HUF) 26.328
FTE (full time equivalent) 9.47
state running project





 

Final report

 
Results in Hungarian
A plazmid mediálta kinolon rezisztencia determinánsok (PMQR): qnr, aac(6')-Ib-cr, oqxAB és qepA gének vizsgálata történt Gram-negatív baktériumokban. Hemokultúrából izolált kiterjedt-spektrumú béta-laktamázt termelő Enterobactericaeae törzsek 75%-a, a vizeletből izolált összes Enterobactericaeae törzseknek pedig 21% hordozott PMQR géneket. A vizeletből izolált kinolon rezisztens Pseudomonas ST773 által akvirált qnrVC kétszeres expressziója a gén potenciális antitoxin hatását indikálta. A szintén vizeletből elsőként izolált qnrD hordozó Morganella morganii törzseket MIC érték alatti ciprofloxacin expozíciónak kitéve a qnrD és a recA gének fokozott expressziója volt megfigyelhető, megerősítve a qnrD gén SOS rendszer által történő szabályozását. Klebsiella törzsekben vizsgálva a PMQR géneket, a levofloxacin és a moxifloxacin MIC értéke a K. pneumoniae ST11 törzsben a qnrB4 és az oqxAB expressziójával, a K. pneumoniae ST307 a qnrB1 és az oqxAB expressziójával korrelált. A qnrA1 hordozó K. oxytoca ST52 minden fluorokinolonnal szemben csökkent érzékenységet mutatott. In vivo egerek gastrointestinális kolonizálása történt aac(6')-Ib-cr hordozó multiresisztens K.pneumoniae törzzsel. A 14 napos per os ciprofloxacin kezelés csökkentette a kolonizáció mértékét, és az általa kiváltott mikrobiom változás csak kis mértékben különbözött a normál flórától.
Results in English
Plasmid-mediated quinolone resistance (PMQR) determinants: qnr genes, aac(6')-Ib-cr, oqxAB, and qepA were investigated in Gram-negative bacteria. 75% of extended-spectrum beta-lacatamase producing Enterobacteriaceae from bloodcultures and 21% of all Enterobactariaceae from urine samples harboured PMQR genes. From urine high-level quinolone resistant Pseudomonas aeruginosa ST773 with acquired qnrVC determinant was isolated and presented a 2-fold increased expression of qnrVC indicating its potential antitoxin role. Also from urine was isolated the first qnrD harbouring Morganella morganii. In M. morganii during sub-MIC ciprofloxacin exposure the elevated expression of qnrD abd recA was observed indicating the SOS dependent regulation of qnrD. Expression of PMQR genes in K. pneumoniae and K. oxytoca strains were also investigated. Levofloxacin and moxifloxacin MIC values correlated in K. pneumoniae ST11 with qnrB4 and oqxAB expression and in K. pneumoniae ST307 with qnrB1 and oqxAB. The qnrA1 carrying K. oxytoca ST52 exhibited reduced susceptibility to all fluoroquinolones. In vivo mice were gastrointestinally colonized by aac(6')-Ib-cr harbouring multi-drug resistant K.pneumoniae. Our new findings is that ciprofloxacin treatment for 14 days can decrease the rate of the gastrointestinal colonization and the ciproflocaxin treatment induced microbiome change showed the less differences from normal flora.
Full text https://www.otka-palyazat.hu/download.php?type=zarobeszamolo&projektid=108481
Decision
Yes





 

List of publications

 
Domokos J, Damjanova E, Kristóf K, Kocsis B, Szabo D: Multiple benefits of plasmid-mediated quinolone resistance determinants in Klebsiella pneumoniae ST11 high-risk clone and recently emerging ST307 clone., Front Microbiol. 2019 Feb 12;10:157. doi: 10.3389/fmicb.2019.00157. eCollection 2019., 2019
Kocsis B, Toth A, Gulyas D, Ligeti B, Katalin K, Rokusz L, Szabo D.: Acquired qnrVC1 and blaNDM-1 in international high-risk Pseudomonas aeruginosa ST773 clone, J. Med. Microbiol: 2019 Mar;68(3):336-338., 2019
Szabó O, Gulyás D, Szabó N, Kristóf K, Kocsis B, Szabó D.: Plasmid-mediated quinolone resistance determinants in Enterobacteriaceae from urine clinical samples., Acta Microbiol Immunol Hung. 2018 Aug 1;65(3):255-265. doi: 10.1556/030.65.2018.012. Epub 2018 Feb 23., 2018
Szabo O, Kocsis B, Szabo N, Kristof K, Szabo D.: Contribution of OqxAB Efflux Pump in Selection of Fluoroquinolone-Resistant Klebsiella pneumoniae., Can J Infect Dis Med Microbiol. 2018 Sep 23;2018:4271638. doi: 10.1155/2018/4271638. eCollection 2018., 2018
Gulyás D, Kocsis B, Szabó D.: Plasmid copy number and qnr gene expression in selection of fluoroquinolone-resistant Escherichia coli., Acta Microbiol Immunol Hung. 22:1-10. doi: 10.1556/030.65.2018.049. [Epub ahead of print], 2018
Kocsis B, Szmolka A, Szabo O, Gulyas D, Kristóf K, Göcző I, Szabo D.: Ciprofloxacin Promoted qnrD Expression and Phylogenetic Analysis of qnrD Harboring Plasmids, Microb Drug Resist. 2018 Nov 21. doi: 10.1089/mdr.2018.0245. [Epub ahead of print], 2018
Kocsis B, Szabo D.: New treatment options for lower respiratory tract infections., Expert Opin Pharmacother. 2017 Sep;18(13):1345-1355. doi: 10.1080/14656566.2017.1363179. Epub 2017 Aug 8., 2017
Sebe I, Kállai-Szabó B, Zelkó R, Szabó D: Polymers and Formulation Strategies of Nanofibrous Systems for Drug Delivery Application and Tissue Engineering, CURR MED CHEM 22: (5) 604-617, 2015
Sebe I, Ostorhazi E, Fekete A, Kovacs NK, Zelko R, Kovalszky I, Li W, Wade JD, Szabo D, Otvos L Jr: Polyvinyl alcohol nanofiber formulation of the designer antimicrobial peptide APO sterilizes Acinetobacter baumannii‑infected skin wounds in mice, Amino Acids 48(1):203-11., 2016
Domokos J, Szabo D, Kristof K: Detection of plasmid-mediated quinolone resistance determinants in extended-spectrum beta-lactamse producing Enterobactericeae strains, Acta Microbiologica et Immunologica Hungarica 2016 Sep;63(3):313-323., 2016
Kocsis B, Kádár B, Tóth Á, Fullár A, Szabó D.: MgrB variants in colistin-susceptible and colistin-resistant Klebsiella pneumoniae ST258., J Microbiol Immunol Infect. 2016 Jul 29. pii: S1684-1182(16)30071-8., 2016
Kocsis B, Domokos J, Szabo D.: Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin., Ann Clin Microbiol Antimicrob. 23;15(1):34., 2016
Domokos J, Szabo D, Kristof K: Detection of plasmid-mediated quinolone resistance determinants in extended-spectrum beta-lactamse producing Enterobactericeae strains, Acta Microbiologica et Immunologica Hungarica 2016 Sep;63(3):313-323., 2016
Kadar B, Kocsis B, Toth A, Kristof K, Felso P, Kocsis B, Boddi K, Szabo D: Colistin resistance associated with outer membrane protein change in Klebsiella pneumoniae and Enterobacter asburiae, ACTA MICROBIOL IMMUNOL HUNG 64: (2) 217-227, 2017
Kocsis B, Kádár B, Tóth Á, Fullár A, Szabó D: MgrB variants in colistin-susceptible and colistin-resistant Klebsiella pneumoniae ST258, J MICROBIOL IMMUNOL 50: (5) 735-736, 2017
Kocsis B, Szabo D: New treatment options for lower respiratory tract infections., EXPERT OPIN PHARMACO 18: (13) 1345-1355, 2017
Ivady B, Kenesei E, Toth-Heyn P, Kertesz G, Tarkanyi K, Kassa C, Ujhelyi E, Mikos B, Sapi E, Varga-Heier K, Guoth G, Szabo D: Factors influencing antimicrobial resistance and outcome of Gram-negative bloodstream infections in children, INFECTION 44: (3) 309-321, 2016
Kocsis B, Szabo D: Zabofloxacin for chronic bronchitis., DRUGS TODAY 52: (9) 495-500, 2016
Ivady B, Szabo D, Damjanova I, Pataki M, Szabo M, Kenesei E: Recurrent outbreaks of Serratia marcescens among neonates and infants at a pediatric department: an outbreak analysis., INFECTION 42: (5) 891-898, 2014
Juhasz J, Kertesz-Farkas A, Szabo D, Pongor S: Emergence of Collective Territorial Defense in Bacterial Communities: Horizontal Gene Transfer Can Stabilize Microbiomes., PLoS One. 2014 Apr 22;9(4):e95511, 2014
Ivady B; Szabo D; Damjanova I; Pataki M; Szabo M; Kenesei E: Recurrent outbreaks of Serratia marcescens among neonates and infants at a pediatric department: an outbreak analysis., Infection PMID: 25015432, 2014
Sebe I, Kállai-Szabó B, Zelkó R, Szabó D: Polymers and Formulation Strategies of Nanofibrous Systems for Drug Delivery Application and Tissue Engineering, CURR MED CHEM 22: (5) 604-617, 2015
Sebe I, Ostorhazi E, Fekete A, Kovacs NK, Zelko R, Kovalszky I, Li W, Wade JD, Szabo D, Otvos L Jr: Polyvinyl alcohol nanofiber formulation of the designer antimicrobial peptide APO sterilizes Acinetobacter baumannii‑infected skin wounds in mice, AMINO ACIDS In press: In press, 2015
Domokos J, Szabo D, Kocsis B, Kristof K: Detection of plasmid-mediated quinolone resistance determinants in extended-spectrum beta-lactamse producing Enterobactericeae strains, Acta Microbiologica et Immunologica Hungarica, 2015





 

Events of the project

 
2016-12-06 14:12:36
Résztvevők változása
2014-02-25 22:46:04
Résztvevők változása




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